WO2021235551A1 - Method for determining resistance against skin aging using genetic polymorphism - Google Patents

Abstract

The purpose of the present invention is to provide a skin test based on SNP analysis, the results of said test being satisfactory for subjects and motivating behavior changes. Provided is a method that comprises evaluating the results of SNP analysis from the viewpoint of resistance against skin aging.

Description

Method for determining resistance to skin aging using gene polymorphisms

The present invention relates to a method for determining resistance to skin aging based on a genetic test, a control program for an evaluation system for skin aging resistance, and a control program for a skin aging resistance evaluation system. Skin counseling is possible based on the method, system, and program for determining the resistance of the skin to aging of the present invention.

In recent years, skin tests based on SNP analysis of genes have been proposed, and the relationship between SNP information and skin quality is being studied, especially for genes encoding proteins that are directly involved in skin quality. As a result, a method for predicting skin characteristics and skin troubles based on the SNP analysis result has been provided. In these studies, SNPs are being investigated for genes that have been shown to be directly involved in skin quality, such as wrinkles and age spots. As such a target gene, for example, MC1R, MMP1, SOD2, GPX1, SIP and the like are targeted. On the other hand, since there are a wide variety of genes that affect the skin characteristics of the skin, the relationship between SNP information and skin characteristics in more genes has also been investigated (Patent Document 1: International Publication No. 2018/101449). issue).

International Publication No. 2018/101449

The skin test based on SNP analysis is performed based on a statistical method between the genetic information regarding the subject's SNP and the measurement data of the skin condition. The skin quality determined based on the subject's SNP information corresponds to the skin condition measurement data used in the statistical method, but the problem is that there is a discrepancy with the evaluation of the skin condition felt by the subject. It has become. The reason is that the skin condition changes not only according to the genetic background but also according to the acquired environmental factors, and the evaluation of the skin quality based on the SNP analysis does not necessarily represent the current skin condition of the subject. Can be mentioned. In addition, since the results of the genetic test reflect the genetic background of the individual, there is a problem that the subject who has undergone the genetic test gives up that the gene cannot be changed.

The present inventors have conducted diligent research on such a problem, and have come to develop a method for evaluating the result of SNP analysis from the viewpoint of resistance to skin aging, instead of using it for evaluation of skin condition. The SNP selected in the present invention is a learning model learned from genetic information, environmental information, and actual skin measurement data, and is generated by a learning model that outputs the skin constitution when genetic information and environmental information are input. This is the SNP adopted in the aging model formula. Therefore, the SNP selected in the present invention is an SNP having a great influence on the aging susceptibility of the skin. It is considered that one of the factors that the skin is easy to age is the low resistance to aging. Therefore, the SNP selected in the present invention is an SNP having a great influence on the resistance of the skin to aging. The resistance of the skin to aging, which is the result of the analysis of the SNPs selected in this way, is an evaluation item corresponding to the genetic background. By evaluating the resistance to aging of the skin based on the SNP selected in the present invention, not only a reasonable evaluation result can be obtained, but also the resistance evaluated to be low can be supplemented by lifestyle and the like. You can appeal what you can do. This can reduce consumer resignation due to genetic factors and provide new value for SNP analysis. In evaluating the resistance to aging of the skin, by dividing the aging of the skin into a plurality of groups, it is possible to evaluate the resistance to aging of each group. Therefore, the present invention relates to the following invention:

[1] A method for determining the resistance to skin aging based on SNP in a gene involved in the resistance to skin aging.
[2] The method according to item 1, wherein the aging of the skin is selected from aging caused by lifestyle, aging caused by the external environment, and natural aging caused by aging.
[3] The resistance to aging of the skin is cell active power, skin shielding power, face shape modeling power, metabolism maintenance power, skin color assist power, stimulation protection power, damage control power, aqua vitamin utilization power, and oil vitamin utilization. The method according to item 1 or 2, wherein the method is at least 1 selected from the group consisting of forces.
[4] An item in which cell active force is determined based on SNP in at least one gene selected from the group consisting of bleomycin hydrolase (BLMH), caspase 14 (CASP14), and hyaluronan synthase 3 (HAS3). The method according to 2 or 3.
[5] The following:
At least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862 determines the resistance to skin aging for cell activity. The method according to item 4.
[6] The method according to item 2 or 3, wherein the skin shielding force is determined based on SNP in at least one gene selected from the group consisting of PLAU (uPA) and CASP14.
[7] The following:
Item 6. The resistance to skin aging with respect to skin shielding is determined by at least one SNP selected from the group consisting of rs2158467, rs2227564, rs2227566, rs2227568, rs2227574, rs3181162, rs4065, rs717309, and rs8110862. Method.
[8] Face shape modeling ability is determined based on SNPs in at least one gene selected from the group consisting of MMP-1, MMP-2, MMP-9, ELN, HAS2, FBRN5, and COL1A1. Or the method according to 3.
[9] The resistance to skin aging is rs1799750, rs10233395, rs1030868, rs1057297, rs1057308, rs1061237, rs1061947, rs1107946, rs1144391, rs13925, rs13969, rs17576, rs17577, rs17804735, rs17855988, rs17884110, rs1800012, rs1871884. Skin for face shape modeling by at least one SNP selected from the group consisting of rs2071307, rs2241145, rs2246416, rs2285053, rs2287074, rs2430347, rs2856728, rs4255143, rs4618701, rs470558, rs5854, rs7149187, rs7201, rs77357345, rs8326, and rs9509. 8. The method of item 8, wherein the resistance to aging of the skin is determined.
[10] The method according to item 2 or 3, wherein the metabolic maintenance ability is determined based on SNP in at least one gene selected from the group consisting of VEGFA and VEGFC.
[11] As the resistance to aging of the skin, the following:
10. The SNPs selected from the group consisting of rs1485766, rs10434, rs2010963, rs475106, rs475920, rs510684, rs699947, rs735286, and rs833061 determine the resistance of skin to aging with respect to metabolic maintenance, according to item 10. Method.
[12] The method according to item 2 or 3, wherein the skin color assisting force is determined based on SNP in at least one gene selected from the group consisting of OCA2 and IRF4.
[13] As the resistance to aging of the skin, the following:
At least one SNP selected from the group consisting of rs1800414, rs1050975, rs1131442, rs12203592, rs12913832, rs1540771, rs1800404, rs1800411, rs74653330, and rs872071 determines the resistance to skin aging with respect to skin color assisting power, item 12. The method described.
[14] The method according to item 2 or 3, wherein the stimulus protection force is determined based on the SNP in at least one gene selected from the group consisting of SOD2 and GPX1.
[15] When the resistance to aging of the skin is a stimulus-protecting force, the following:
At least one SNP selected from the group consisting of rs4880, rs10370, rs1050450, rs1800668, rs3448, rs3811699, rs732498, rs7855, rs8031 and rs8179164 determines the resistance to skin aging with respect to irritation protection, in item 14. The method described.
[16] The method of item 2 or 3, wherein the damage control force is determined based on the SNP in at least one gene selected from the group consisting of TNF-α, PLAU (uPA), and TNFR2.
[17] As the resistance to aging of the skin, the following:
With at least one SNP selected from the group consisting of rs1799724, rs1061622, rs1800629, rs2227564, rs2227566, rs2227568, rs2227574, rs235249, rs3093662, rs3397, rs361525, rs4065, rs472093, rs474247, and rs673, for skin aging related to damage control. The method of item 16, wherein the resistance is determined.
[18] The item 2 or 3, wherein the aquavitamin utilization ability is determined based on SNP in at least one gene selected from the group consisting of genes related to the control of vitamin B2 level and vitamin B12 level in blood. Method.
[19] As the resistance to aging of the skin, the following:
18. The method of item 18, wherein the resistance to skin aging with respect to aquavitamin utilization is determined by at least one SNP selected from the group consisting of rs1801133, rs1047781, rs10515552, rs2298585, and rs3760776.
[20] Oil vitamin utilization is determined based on SNP in at least one gene selected from the group consisting of genes related to the control of vitamin A level, vitamin D level, and vitamin E level in blood. Or the method according to 3.
[21] As the resistance to aging of the skin, the following:
At least one SNP selected from the group consisting of rs10882272, rs11057830, rs11234027, rs12272004, rs12785878, rs12934922, rs1667255, rs1993116, rs2060793, rs2108622, rs2282679, rs7501331 and rs964184 provides resistance to skin aging for oil vitamin utilization. The method according to item 20, which is determined.
[22] A method for proposing preventive measures against aging according to the resistance determined by the method according to any one of items 1 to 21.
[23] Multiple selected from the group consisting of cell active power, skin shielding power, face shape modeling power, metabolism maintenance power, skin color assist power, stimulus protection power, damage control power, aqua vitamin utilization power, and oil vitamin utilization power. 22. The method of item 22, wherein the resistance is determined and the corresponding preventive action is proposed for at least one resistance determined to be low.
[24] A device for determining the resistance of skin to aging.
Input section for inputting SNP information about genes involved in skin aging resistance,
A storage unit that stores the relationship between SNP information and the resistance of the skin to aging in advance.
A processing unit that compares the SNP information input from the input unit with the relationship between the SNP information stored in the storage unit in advance and the resistance to skin aging, and determines the resistance to skin aging.
The determination device comprising an output unit that outputs a determined resistance to skin aging.
[25] The resistance to aging of the skin is cell active power, skin shielding power, face shape modeling power, metabolism maintenance power, skin color assist power, stimulation protection power, damage control power, aqua vitamin utilization power, and oil vitamin utilization. The determination device according to item 24, which is at least one selected from the group consisting of forces.
[26] The gene involved in cell active force is at least one gene selected from the group consisting of BLMH, CASP14, and HAS3.
The gene involved in the skin shielding force is at least one gene selected from the group consisting of PLAU (uPA) and CASP14.
The gene involved in face shape modeling ability is at least one gene selected from the group consisting of MMP-1, MMP-2, MMP-9, ELN, HAS2, FBRN5, and COL1A1.
The gene involved in metabolic maintenance is at least one gene selected from the group consisting of VEGFA and VEGFC.
The gene involved in skin color assisting power is at least one gene selected from the group consisting of OCA2 and IRF4.
The gene involved in stimulus protection is at least one gene selected from the group consisting of SOD2 and GPX1.
The gene involved in damage control is at least one gene selected from the group consisting of TNF-α, PLAU (uPA), and TNFR2.
The gene involved in aquavitamin utilization is at least one gene selected from the group consisting of genes related to the control of vitamin B2 level and vitamin B12 level in blood, and the gene involved in oil vitamin utilization is in the blood. 25. The determination device according to item 25, which is at least one gene selected from the group consisting of genes related to the control of Vitamin A level, Vitamin D level, and Vitamin E level.
[27] SNP information on genes involved in cell active force is as follows:
Information about at least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862.
SNP information about genes involved in skin shielding is as follows:
Information about at least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862.
SNP information about genes involved in face shape modeling ability is as follows:
rs1799750, rs10233395, rs1030868, rs1057297, rs1057308, rs1061237, rs1061947, rs1107946, rs1144391, rs13925, rs13969, rs17576, rs17577, rs17804735, rs17855988, rs17884110, rs1800012, rs1871884, rs2046571 Information about at least one SNP selected from the group consisting of rs2856728, rs4255143, rs4618701, rs470558, rs5854, rs7149187, rs7201, rs77357345, rs8326, and rs9509.
SNP information about genes involved in metabolic maintenance is as follows:
Information about at least one SNP selected from the group consisting of rs1485766, rs10434, rs2010963, rs475106, rs475920, rs510684, rs699947, rs735286, and rs833061.
SNP information about genes involved in skin color assisting power is as follows:
Information about at least one SNP selected from the group consisting of rs1800414, rs1050975, rs1131442, rs12203592, rs12913832, rs1540771, rs1800404, rs1800411, rs74653330, and rs872071.
SNP information about genes involved in stimulus protection is as follows:
Information about at least one SNP selected from the group consisting of rs4880, rs10370, rs1050450, rs1800668, rs3448, rs3811699, rs732498, rs7855, rs8031 and rs8179164.
SNP information about genes involved in damage control is as follows:
Information about at least one SNP selected from the group consisting of rs1799724, rs1061622, rs1800629, rs2227564, rs2227566, rs2227568, rs2227574, rs235249, rs3093662, rs3397, rs361525, rs4065, rs472093, rs474247, and rs673.
SNP information on genes involved in aquavitamin utilization is as follows:
Information about at least one SNP selected from the group consisting of rs1801133, rs1047781, rs10515552, rs2298585, and rs3760776.
SNP information on genes involved in oil-vitamin utilization is as follows:
The decision according to item 25 or 26, which is information about at least one SNP selected from the group consisting of rs10882272, rs11057830, rs11234027, rs12272004, rs12785878, rs12934922, rs1667255, rs1993116, rs2060793, rs2108622, rs2282679, rs7501331 and rs964184. Device.
[28] The memory unit further memorizes preventive measures according to the resistance of the skin to aging.
The processing unit reads out the preventive measures according to the resistance determined in the processing unit from the storage unit.
The determination device according to any one of items 24 to 27, wherein the output unit outputs the read preventive action.
[29] The processing unit of the determination device has cell active power, skin shielding power, face shape modeling power, metabolism maintenance power, skin color assist power, stimulus protection power, damage control power, aqua vitamin utilization power, and oil vitamin utilization. 28. Item 28, wherein a plurality of resistances selected from the group consisting of forces are determined, and the output unit of the determination device outputs a corresponding preventive measure for at least one resistance determined to have low resistance. Determination device.
[30] A program that causes a computer including an input unit, a storage unit, a processing unit, and an output unit to determine the resistance to skin aging, and is described as follows:
The processing unit is made to compare the SNP information about the genes involved in the resistance to skin aging input from the input unit with the relationship between the SNP information previously stored in the storage unit and the resistance to skin aging. A command that determines the resistance of the skin to aging;
The program comprising a command to output the determined resistance to skin aging from the output unit.
[31] The resistance to aging of the skin is cell active power, skin shielding power, face shape modeling power, metabolism maintenance power, skin color assist power, stimulus protection power, damage control power, aqua vitamin utilization power, and oil vitamin utilization. The program according to item 30, wherein the program is at least one selected from the group consisting of forces.
[32] The gene involved in cell active force is at least one gene selected from the group consisting of BLMH, CASP14, and HAS3.
The gene involved in the skin shielding force is at least one gene selected from the group consisting of PLAU (uPA) and CASP14.
The gene involved in face shape modeling ability is at least one gene selected from the group consisting of MMP-1, MMP-2, MMP-9, ELN, HAS2, FBRN5, and COL1A1.
The gene involved in metabolic maintenance is at least one gene selected from the group consisting of VEGFA and VEGFC.
The gene involved in skin color assisting power is at least one gene selected from the group consisting of OCA2 and IRF4.
The gene involved in stimulus protection is at least one gene selected from the group consisting of SOD2 and GPX1.
The gene involved in damage control is at least one gene selected from the group consisting of TNF-α, PLAU (uPA), and TNFR2.
The gene involved in aquavitamin utilization is at least one gene selected from the group consisting of genes related to the control of vitamin B2 level and vitamin B12 level in blood.
The program according to item 31, wherein the gene involved in the ability to utilize oil vitamins is at least one gene selected from the group consisting of genes related to the control of vitamin A level, vitamin D level, and vitamin E level in blood. ..
[33] SNP information about genes involved in cell active force is as follows:
Information about at least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862.
SNP information about genes involved in skin shielding is as follows:
Information about at least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862.
SNP information about genes involved in face shape modeling ability is as follows:
rs1799750, rs10233395, rs1030868, rs1057297, rs1057308, rs1061237, rs1061947, rs1107946, rs1144391, rs13925, rs13969, rs17576, rs17577, rs17804735, rs17855988, rs17884110, rs1800012, rs1871884, rs2046571 Information about at least one SNP selected from the group consisting of rs2856728, rs4255143, rs4618701, rs470558, rs5854, rs7149187, rs7201, rs77357345, rs8326, and rs9509.
SNP information about genes involved in metabolic maintenance is as follows:
Information about at least one SNP selected from the group consisting of rs1485766, rs10434, rs2010963, rs475106, rs475920, rs510684, rs699947, rs735286, and rs833061.
SNP information about genes involved in skin color assisting power is as follows:
At least one SNP selected from the group consisting of rs1800414, rs1050975, rs1131442, rs12203592, rs12913832, rs1540771, rs1800404, rs1800411, rs74653330, and rs872071.
Information about
SNP information about genes involved in stimulus protection is as follows:
Information about at least one SNP selected from the group consisting of rs4880, rs10370, rs1050450, rs1800668, rs3448, rs3811699, rs732498, rs7855, rs8031 and rs8179164.
SNP information about genes involved in damage control is as follows:
Information about at least one SNP selected from the group consisting of rs1799724, rs1061622, rs1800629, rs2227564, rs2227566, rs2227568, rs2227574, rs235249, rs3093662, rs3397, rs361525, rs4065, rs472093, rs474247, and rs673.
SNP information on genes involved in aquavitamin utilization is as follows:
Information about at least one SNP selected from the group consisting of rs1801133, rs1047781, rs10515552, rs2298585, and rs3760776.
SNP information on genes involved in oil-vitamin utilization is as follows:
The program according to item 31 or 32, which is information about at least one SNP selected from the group consisting of rs10882272, rs11057830, rs11234027, rs12272004, rs12785878, rs12934922, rs1667255, rs1993116, rs2060793, rs2108622, rs2282679, rs7501331 and rs964184. ..
[34] The program is as follows:
A command to memorize preventive measures according to the resistance of the skin to aging in the memory unit,
A command to operate the processing unit to read the preventive action according to the resistance determined in the processing unit from the storage unit,
The program according to any one of items 30 to 33, further comprising a command to output the read action to the output unit.
[35] The program consists of a computer with cell activation power, skin shielding power, face shape modeling power, metabolism maintenance power, skin color assist power, stimulus protection power, damage control power, aqua vitamin utilization power, and oil vitamin utilization power. A command to determine multiple resistances selected from the group,
34. The program of item 34, comprising a command to output a corresponding preventive action for at least one resistance determined by the processing unit to be low resistance.

By evaluating the results of SNP analysis from the viewpoint of resistance to aging, it is possible to make an appropriate evaluation according to the genetic background and to propose appropriate preventive measures to supplement the resistance.

FIG. 1A is a diagram schematically showing an information processing apparatus including an input unit, a storage unit, a processing unit, and an output unit. FIG. 1B is a diagram schematically showing a system in which an information processing apparatus operates via a network. 2A to 2B are schematic views showing a flow for the information processing apparatus of the present invention to determine the resistance to aging of the skin according to a program. 2C to 2D are schematic views showing a flow for the information processing apparatus of the present invention to determine the resistance to aging of the skin according to a program. FIG. 3 shows a graph in which objects belonging to a certain ratio of the high price side and the low price side are classified into a high price group and a low price group from the measured values of the skin condition (wrinkles). FIG. 4 is a graph of the ROC curve showing the relationship between sensitivity and specificity, which was created when the learning model for determining the skin constitution was verified.

The present invention relates to a method for determining the resistance of a skin to aging based on the SNP information of a subject. As the SNP information of the subject, information about one or more SNPs in the gene involved in the resistance of the skin to aging can be used.

The skin condition changes with aging, and the degree of skin aging is affected by the genetic background. As for the skin condition, spots, wrinkles, skin elasticity, melanin amount, skin brightness, yellowing, upper arm skin color, etc. change with aging. The resistance of the skin to aging refers to the ability to delay the progression of aging and depends on the genetic background. That is, the progress of aging is affected by the accumulation of changes caused in the living body in daily life represented by aging, and also by external environmental factors such as ultraviolet rays and dryness. The resistance to such internal and external effects of promoting skin aging varies from individual to individual due to their genetic background. Therefore, knowing the resistance of the skin to aging based on the genetic background means knowing the resistance to the effects of acquired internal and external skin aging-promoting factors. Since the internal and external skin aging-promoting factors have a wide range of effects on the skin, the skin aging resistance that affects the responsiveness of the skin is set and added to each individual to prevent individual skin aging. Resistance is determined. In the present invention, the resistance to skin aging determined based on the SNP information of the subject refers to the resistance to skin aging based on the genetic background.

Acquired factors that affect skin aging include internal lifestyle habits such as stress and nutritional status such as disordered eating habits, and external factors such as ultraviolet rays and dryness. When the resistance to aging of the skin evaluated by the genetic background is low, it is possible to delay the aging of the skin by changing the acquired environmental factors, that is, the lifestyle and the external environment. Lifestyles involved in skin aging include eating habits, sleep rhythms, excessive exercise, or lack of exercise. Examples of the external environment involved in skin aging include ultraviolet rays, pollutants, gravity, and changes in the temperature and humidity of living spaces.

If it is determined by SNP analysis that the resistance to skin aging caused by lifestyle is low, improvement of lifestyle can be instructed. In addition, if SNP analysis determines that the resistance to aging of the skin caused by the external environment is low, preventive measures to weaken the influence of the external environment, such as UV care, measures against pollutants, and care against gravity such as massage. It can be performed. By classifying the types of skin aging in this way and evaluating the resistance to skin aging corresponding to the classified skin aging, it is possible to perform appropriate treatments for the classified skin aging. ..

In the present invention, the SNP involved in determining the resistance to skin aging is a skin aging model set by machine learning the relationship between the genetic information and environmental information regarding the subject's SNP and the measurement data of the skin condition. The SNP adopted in the formula is used. From the SNP adopted in the skin aging model formula, genes involved in skin function are clarified by dermatological research, genes involved in aging resistance are selected, and groups are grouped by function. SNPs that affect the function of genes selected through this selection process can exhibit resistance to skin aging with respect to grouped functions.

The SNP used in the present invention includes the following:
rs1050565, rs8110862, rs2232228, rs2227564, rs1799750, rs7201, rs17577, rs8326, rs2046571, rs2246416, rs1107946, rs2010963, rs1485766, rs1800414, rs1540771, rs4880, rs1050450, rs1799724, rs1061622, rs1801133 rs2158467, rs3785079, rs4065, rs5854, rs2241145, rs9509, rs2071307, rs1057308, rs7149187, rs1057297, rs833061, rs475106, rs74653330, rs12203592, rs7855, rs3448, rs1800629, rs3397, rs1047781 rs2227566, rs470558, rs1030868, rs13925, rs2856728, rs1871884, rs2430347, rs1061237, rs699947, rs12913832, rs872071, rs8031, rs1800668, rs361525, rs235249, rs3760776, rs12934922, rs12785878, rs11057830, rs3103308437 rs13969, rs10233395, rs4255143, rs17804735, rs1061947, rs10434, rs475920, rs1800404, rs1050975, rs10370, rs3811699, rs673, rs472093, rs10515552, rs7501331, rs1993116, rs12272004, rs3190884, rs2227574, rs17884110 rs1800012, rs735286, rs510684, rs1800411, rs11 At least one selected from the group consisting of 31442, rs732498, rs8179164, rs3093662, rs474247, rs2060793, may be used. From the listed SNPs, it can be arbitrarily selected according to the resistance of the skin to be evaluated to aging.

In one aspect of the present invention, the resistance to skin aging in the present invention is cell active power, skin shielding power, face shape modeling power, metabolism maintenance power, skin color assist power, stimulus protection power, damage control power, aquavitamin. At least one resistance selected from the group consisting of utilization ability and oil vitamin utilization ability.

Cell active power can be said to be moisturizing power, anti-aging moisturizing power, cell homeostasis power, cell environment maintenance power, cell metabolism regulation power, skin metabolism power, and skin moisturizing power, and properly maintains the water content of the skin stratum corneum. It is a power to enhance work. .. By properly maintaining the water content of the skin stratum corneum, the action of enzymes in the stratum corneum is maintained, and skin metabolism and homeostasis are maintained. Moisture in the stratum corneum also contributes to the softness of the skin and alleviates the effects of facial expression on the shape of the skin surface. Moisture in the stratum corneum, which is so important, can be increased by increasing the production of natural moisturizing factors (NMFs), thereby normalizing epidermal differentiation and enhancing barrier function. Examples of genes involved in cell active force include bleomycin hydrolase (BLMH), caspase 14 (CASP14), and hyaluronan synthase 3 (HAS3). As the SNP related to cell active force, at least one selected from the group consisting of the following: rs1050565, rs1552472, rs2129785, rs3103308, rs3190884, rs8110862, rs2158467, rs3181162, rs717309, rs2158467, rs2232228, rs3785079, rs2232227, rs3759981, rs3785079 is used. Can be done. In one embodiment, any combination of such SNPs, and optionally all combinations, can be used to determine the resistance of the skin to aging due to moisturizing power. The relationship between each SNP and the gene is shown in the table below.

The skin shielding power can also be said to be barrier power, anti-aging barrier defense power, skin wrapping power, skin internal stabilization power, skin gate power, and skin gate keeping power to prevent skin moisture from leaking to the outside. , It is the power to keep the barrier function good so that substances that have an adverse effect from the outside cannot easily enter. By normalizing epidermal differentiation and normally constructing the stratum corneum, the barrier function is maintained well. Examples of genes involved in skin shielding power include urokinase-type plasminogen activator (uPA) and caspase 14 (CASP14). As the SNP related to the skin shielding force, at least one selected from the group consisting of the following: rs2227564, rs4065, rs2227566, rs2227568, rs2227574, rs8110862, rs2158467, rs3181162, rs717309, rs2158467 can be used. In one embodiment, any combination of such SNPs, and optionally all combinations, can be used to determine the resistance of the skin to aging with respect to barrier function. The relationship between each SNP and the gene is shown in the table below.

The facial shape modeling force can also be referred to as skin internal structural force, face shape-up force, firmness-up force, and skin foaming force, and its constituent elements are anti-aging dermis epidermis cooperation force and anti-aging dermis elastic assisting force. The anti-aging dermis epidermis cooperation ability can be said to be the ability to keep the skin layer and the ability to communicate with the skin, and refers to the ability to maintain the basement membrane at the boundary between the epidermis and the dermis and improve the function of the skin. Further, the anti-aging dermis elastic assist force can be said to be a skin spring adjusting force and a skin spring force, and is a force for maintaining the dermis structure that maintains the elasticity of the skin. Matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), elastin (ELN), hyaluronan synthase as genes involved in facial shape modeling ability Examples include enzyme 2 (HAS2), fibrin 5 (FBRN5), and type I collagen (COL1A1). SNPs related to face shape modeling ability include: rs1799750, rs5854, rs470558, rs1144391, rs17884110, rs7201, rs2241145, rs1030868, rs2285053, rs2287074, rs17577, rs9509, rs13925, rs13969, rs17576, rs8326, rs2071307, rs2856728, rs. At least one selected from the group consisting of rs17855988, rs2046571, rs1057308, rs1871884, rs4255143, rs4618701, rs2246416, rs7149187, rs2430347, rs17804735, rs77357345, rs1107946, rs1057297, rs1061237, rs1061947, rs1800012 can be used. In one embodiment, any combination of such SNPs, and optionally all combinations, can be used to determine resistance to aging due to anti-aging dermal epidermal coordination and anti-aging dermal elastic assisting forces. The relationship between each SNP and the gene is shown in the table below.

Metabolism maintenance power can also be said to be circulation power, anti-aging circulation regulation power, circulation support power, circulation maintenance power, holistic cooperation power, skin nutrition supply power, and lymph that removes blood vessels and waste products that supplement nutrition. It is the power to improve. Examples of genes involved in metabolic maintenance include vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor C (VEGFC). As the SNP involved in metabolic maintenance, at least one selected from the group consisting of the following: rs2010963, rs833061, rs699947, rs10434, rs735286, rs1485766, rs475106, rs475106, rs475920, rs510684 can be used. In one embodiment, any combination of such SNPs, and optionally all combinations, can be used to determine resistance to aging caused by blood vessels and lymph. The relationship between each SNP and the gene is shown in the table below.

Skin color assist power can also be said to be skin color adjustment power, anti-aging skin color adjustment power, UV filter power, skin color maintenance power, UV response power, photoaging response power, and high melanin, which has a natural UV protection function in the skin. It is the power to keep. Genes involved in skin color assisting power include oculocutaneous albinism type II (OCA2) and interferon regulator (IRF4). As the SNP related to the skin color assisting power, at least one selected from the group consisting of the following: rs1800414, rs74653330, rs12913832, rs1800404, rs1800411, rs1540771, rs12203592, rs872071, rs1050975, rs1131442 can be used. In one embodiment, any combination of such SNPs, and optionally all combinations, can be used to determine resistance to melanin-induced aging. The relationship between each SNP and the gene is shown in the table below.

The stimulus protection power can also be said to be antioxidant power, anti-aging oxidative power, stimulus scavenging power, stimulus sedative power, damage blocking power, and damage absorbing power, and is the power to detoxify and remove active oxygen generated in the skin. be. Reactive oxygen species are removed intracellularly by the action of enzymes such as superoxide dismutase and glutathione peroxidase. Examples of genes involved in stimulus protection include superoxide dismutase-2 (SOD2) and glutathione peroxidase 1 (GPX1). As the SNP related to the stimulus protection power, at least one selected from the group consisting of the following: rs4880, rs7855, rs8031, rs10370, rs732498, rs1050450, rs3448, rs1800668, rs3811699, rs8179164 can be used. In one embodiment, any combination of such SNPs, and optionally all combinations, can be used to determine resistance to aging due to anti-aging oxidative power. The relationship between each SNP and the gene is shown in the table below.

The damage control power can also be said to be inflammation control power, anti-aging anti-inflammatory power, inflammation control power, skin internal calming power, damage fire extinguishing power, and skin attack control power, and reduces or suppresses the production of inflammatory factors in the skin. It is power. Inflammation can be suppressed by reducing inflammatory factors. Genes involved in damage control ability include tumor necrosis factor α (TNFα), urokinase-type plasminogen activator (PLAU (uPA)), and tumor necrosis factor receptor 2 (TNFR2). As the SNP related to damage control power, at least one selected from the group consisting of the following: rs1799724, rs1800629, rs361525, rs673, rs3093662, rs2227564, rs4065, rs2227566, rs2227568, rs2227574, rs1061622, rs3397, rs235249, rs472093, rs474247 is used. Can be done. In one embodiment, any combination of such SNPs, and optionally all combinations, can be used to determine resistance to aging due to inflammation. The relationship between each SNP and the gene is shown in the table below.

The ability to utilize aqua vitamins can be said to be anti-aging water-soluble vitamin control ability, aqua vitamin optimization ability, and aqua vitamin adjustment ability, and is the ability to normalize the blood concentration of water-soluble vitamins. Genes involved in aquavitamin utilization include genes that affect the control of blood levels of vitamin B2 and vitamin B12. As the SNP related to the aquavitamin utilization ability, at least one selected from the group consisting of the following: rs1801133, rs2298585, rs1047781, rs3760776, rs10515552, rs3760776 can be used. In one embodiment, any combination of such SNPs, and optionally all combinations, can be used to determine resistance to aging due to aquavitamin blood levels. The relationship between each SNP and the gene is shown in the table below.

The ability to utilize oil vitamins can be said to be anti-aging oil-soluble vitamin control ability, oil vitamin optimization ability, and oil vitamin adjustment ability, and is the ability to normalize the blood concentration of fat-soluble vitamins. Genes involved in the ability to utilize oil vitamins include genes that affect the control of blood levels of vitamin A, vitamin D, and vitamin E. As the SNP related to the ability to utilize oils and vitamins, at least one selected from the group consisting of the following: rs10882272, rs1667255, rs12934922, rs7501331, rs2282679, rs11234027, rs12785878, rs1993116, rs2060793, rs2108622, rs964184, rs11057830, rs12272004 can be used. In one embodiment, any combination of such SNPs, and optionally all combinations, can be used to determine resistance to aging due to oil vitamin blood levels. The relationship between each SNP and the gene is shown in the table below.

In another aspect of the invention:
Input section for inputting SNP information,
A storage unit that stores the relationship between SNP information and the resistance of the skin to aging in advance.
A processing unit that determines the resistance to skin aging by comparing the SNP information input from the input unit with the relationship between the SNP information stored in advance in the storage unit and the resistance to skin aging, and the determined unit. It relates to a device for determining the resistance to skin aging, including an output unit that outputs the resistance to skin aging. The SNP information used in the determination device of the present invention may be the same as the SNP information used in the method of the present invention.

In yet another aspect, the invention is a program that causes a computer to determine resistance to skin aging, including: input, storage, processing, and output:
A command to have the processing unit compare the relationship between the SNP information input from the input unit, the SNP information stored in the storage unit in advance, and the resistance to skin aging, and determine the resistance to skin aging; It also relates to a program that includes a command to output the determined resistance to skin aging from the output section. The SNP information used in the program of the present invention may be the same as the SNP information used in the method of the present invention.

In determining the resistance to aging of the skin in the method, determination device, and program of the present invention, the genotype (major homotype: Homo1, heterotype: Hetero,) was selected for each SNP for each resistance to aging. Minor homozygotes: Scores can be determined based on Homo2). The table below shows the correspondence between major homozygotes (Homo1), phenotypes, and genetic models of each gene in SNP.

When the SNP of a certain gene is a major homozygous and increases resistance, it is described as Homo1: high, and when it decreases resistance, it is described as Homo1: low. For heterozygotes, four genetic models (Dominant, Recessive, Additive, Multiplicative) selected for each SNP using the skin constitution results among the analysis results obtained in the relationship study between skin quality and gene SNP (Dominant, Recessive, Additive, Multiplicative) Calculate the frequency of and adopt the model that appears most frequently. The score can be arbitrarily determined according to the strength of the resistance in each model. As an example, for SNPs whose resistance is reduced in the major homozygous type, the resistance in each genetic model is expressed as shown in the table below and scored respectively.

The method, determination device, and / or program of the present invention has cell active power, skin shielding power, face shape modeling power, metabolic maintenance power, skin color assisting power, stimulus protection power, damage control power, aquavitamin utilization power, and oil. It is possible to determine the resistance to aging of at least one skin selected from the group consisting of vitamin utilization. The method, determination device, and / or program of the present invention can determine the resistance to a plurality of skin aging among the above-mentioned resistance to skin aging. More preferably, it determines the resistance of 2, 3, 4, 5, 6, 7, 8 or 9 to skin aging. Prophylactic measures against aging can be provided depending on the resistance to aging determined by the methods, determination devices, and / or programs of the present invention. Of the plurality of determined skin resistance to aging, more preferably, the one having the lowest score for resistance to aging can be selected in order to provide preventive measures. If the scores are equivalent, the resistance to aging to be selected can be determined based on the results of a separately obtained questionnaire. Since the resistance to aging displayed in this way is genetically weak resistance, it is necessary to take priority measures.

In the present invention, the SNP is represented by an rs number (Reference SNP ID number). Detailed information on SNPs (positions and mutations on chromosomes) corresponding to each rs number is managed by the National Center for Biotechnology Information (NCBI), and is managed by the NCBI homepage ( http://www.ncbi.nlm.). It can be referred to in nih.gov /).

SNP detection may be performed by any known method. As an example, a subject's nucleic acid is purified from a subject's biological sample such as saliva, blood, mucous membrane, tissue piece, hair, etc. according to a conventional method, and SNP is detected in the purified nucleic acid. Therefore, the method for determining skin characteristics of the present invention may further include a sample preparation step and a nucleic acid purification step. The nucleic acid may be DNA or RNA, and in the case of RNA, it is preferable to perform reverse transcription after purification to prepare DNA. In the SNP detection step, any method can be used as long as it is a method that enables detection of SNP in purified nucleic acid. SNPs can be detected by sequencing around the position of the target SNP, or by using a PCR-based method, a DNA probe method, or a mass spectrometry method. You can also. Examples of PCR-based methods include SNP typing method, TaqMan PCR method, single nucleotide extension method, Pyrosequencing method, and Exonuclease Cycling Assay method. Examples of the method using a DNA probe include a DNA chip method (DNA microarray) and an Invader method (Comprehensive Gene Polymorphism Analysis (SNP) Nikkei Journal, 125, 148-152, 2005). An SNP may be accompanied by another SNP that is in linkage disequilibrium. The target SNP can be detected by detecting the SNP that is in linkage disequilibrium with the target SNP. Therefore, in the present invention, the detection of SNP is not limited to directly detecting the target SNP, but also includes detecting the target SNP by detecting the SNP in linkage disequilibrium. And.

It is also possible to detect the presence of SNP based on the base sequence of an individual whose sequence has already been determined. In this case, the presence of the SNP can be detected by examining the sequence at the position where the SNP exists in the data of the base sequence already determined. Therefore, the detection of the SNP in this case may be performed by inputting the base sequence data to the computer in which the SNP information is stored. In a more preferred embodiment, the input is input from the terminal via the Internet, the SNP is detected on the server, and the detection result can be output to the terminal via the Internet.

FIG. 1A shows a specific configuration of a determination device of the present invention including an input unit 11, a storage unit 12, a processing unit 13, and an output unit 14. The determination device of the present invention may be the information processing device 10 or may form a system 20 connected to the information processing device 10 via a network (FIG. 1B). In the system 20, a terminal 30 exists separately from the information processing device 10, and is connected to the information processing device 10 via a network. The connection between the terminal 30 and the information processing device 10 may be wired or wireless. As an example, it may be connected via an intranet or the Internet.

The input unit 11 further includes an interface for any device that enables data input. It may be connected to an external storage device such as a keyboard, an operation unit such as a mouse, a communication unit, a CD-ROM, a DVD-ROM, a BD-ROM, or a memory stick via an interface. Information is input to the information processing device via the input unit 11. The information input from the input unit may include a command or the like in addition to the SNP information. Information about the SNP may be input from the input unit 11 and stored in the storage unit 12. Instead of the information about the SNP, the genetic sequence information of the target may be input from the input unit 11. The input sequence information may be temporarily stored in the storage unit 12 or may be sent to the processing unit 13 as it is. The genetic sequence information of the target may be the whole genome sequence of the target, only a partial sequence of interest, or only SNP information. Processing instructions in the processing unit 13 can be given from the input unit 11 via the operation unit.

The storage unit 12 includes, for example, a memory device such as a RAM, ROM, or a flash memory, a fixed disk device such as a hard disk drive, or a portable storage device such as a flexible disk or an optical disk, with respect to any device for storing data. .. The storage unit 12 stores data and instructions input from the input unit 11, programs used for various processing of the computer, processing results by the processing unit 13, a database, a form to be output to the output unit 14, and the like. The computer program may be installed via a computer-readable recording medium such as a CD-ROM or a DVD-ROM, or via the Internet. The computer program is installed in the storage unit 12 using a known setup program or the like. The storage unit 12 stores the relationship between the SNP information and the resistance of the skin to aging. In addition, a table or mathematical formula for scoring the resistance of the skin to aging is stored. The relationship with preventive measures against skin aging resistance according to the score may also be remembered. In addition, the storage unit 12 may store information about the results of a questionnaire regarding skin problems.

The processing unit 13 is an arbitrary device that performs arithmetic processing, and usually has one or a plurality of processors or peripheral circuits thereof. The processing unit 13 comprehensively controls the overall operation of the information processing device 10, and is, for example, a central processing unit (CPU). The processing unit 13 executes various arithmetic processes according to the program stored in the storage unit 12. The arithmetic processing is performed by the processor included in the processing unit 13. This processor includes a functional module that controls an input unit 11, a storage unit 12, and an output unit 14, and can perform various controls. Each of these parts may be composed of independent integrated circuits, microprocessors, firmware, and the like. The processing unit 13 reads out the relationship between the SNP information input from the input unit 11 and the SNP information stored in the storage unit 12 and the resistance to skin aging, and determines the resistance to skin aging. The resistance may be determined by reading out and scoring a table or mathematical formula for scoring the resistance of the skin to aging stored in the storage unit 12. Score the resistance to aging of multiple skins and take preventive measures for the resistance to aging of a given number of, eg, 1, 2, 3, or 4, preferably 3 low-scoring skins. It can be read from and determined. When the scores are the same, the processing unit 13 further reads out the results of the separately acquired questionnaire for skin problems from the storage unit 12, and determines which one should be selected for the resistance to aging of the skin having the same score. be able to. Specifically, select the resistance to skin aging, which is highly related to skin problems. The processing unit 13 can also operate to detect the presence of the SNP in the genetic sequence information when the target genetic sequence information is input instead of the SNP information. More specifically, the processing unit 13 detects the presence of the SNP in the target sequence information from the sequence information of the SNP stored in advance in the storage unit 12 and the target sequence information input from the input unit 11. be able to. Information about the existence of the SNP detected by the processing unit 13 may be temporarily stored in the storage unit 12.

The output unit 14 is an arbitrary device capable of outputting the processing result by the processing unit 13, for example, a display device such as a liquid crystal display that directly displays the result, an output means such as a printer, and may include an interface. It may be connected to a communication unit or an external storage device for output via a network via an interface. The communication unit used in the input unit 11 and the output unit 14 relates to a communication interface such as a LAN or a port for connecting an information processing device to a network. The output unit 14 outputs, for example, the resistance to aging of the skin of the subject as a result of the processing by the processing unit 13. Further, the output unit 14 outputs SNP information possessed by the subject and preventive measures for those having low resistance to skin aging.

Counseling can be performed based on the resistance of the skin to aging output from the output unit 14. In counseling, preventive and strengthening measures can be provided according to the resistance of the skin to aging. "Depending on the resistance of the skin to aging" is to provide a treatment that can supplement the resistance when the resistance is low. The relationship between the resistance to skin aging and the preventive measures may be stored in the storage unit 12 in advance, and the output unit 14 outputs the information on the preventive measures together with the output of the resistance to the skin aging. be able to. As the preventive treatment, in addition to cosmetic treatments such as the frequency and method of use of cosmetics and ingredients, treatments that change lifestyle habits and the external environment may be used.

It is possible to provide preventive measures according to the resistance of each skin to aging evaluated by the method, device or program of the present invention. Such preventive measures can be proposed not only for cosmetics and other cosmetic treatments that are directly applied to the skin and how to use them, but also for behaviors such as food, sleep, exercise, bathing, and mental activity. For subjects evaluated to have weak cell activity, treatments to increase cell activity can be proposed. Such treatments include cosmetological treatments such as facial masks and beauty treatments, products that enhance water retention, use of humidifiers, exercise to improve blood circulation, and meditation that is effective for moisturizing. Can be mentioned. For subjects evaluated as having weak skin shielding power, treatments to enhance skin shielding power can be proposed. Such measures include measures to reduce stress such as aroma, products for reviewing sleep time and recovery from fatigue, diets rich in ω3 oil and minerals, and intestinal activity. For subjects evaluated as having weak face shape modeling ability, it is possible to propose a procedure for enhancing face shape modeling ability. Such procedures include facial muscle exercises such as massage and face yoga, drinking collagen drinks, protein-rich diets, and the use of products that avoid blue light. For subjects evaluated as having weak metabolic maintenance ability, treatments to enhance metabolic maintenance ability can be proposed. Such treatments include cosmetological measures that promote blood circulation and improve lymphatic flow, exercise such as hot yoga and kaatsu training, ginger that promotes blood circulation, a diet rich in vitamins A and E, and sleeping methods that suppress swelling. Can be mentioned. For subjects evaluated as having weak skin color assisting power, it is possible to propose a treatment for enhancing skin color assisting power. Such measures include the use of sunscreen goods such as sunscreens and parasols, meals containing a large amount of green-yellow vegetables and nuts to prevent photoaging, and indoor sun bathing in the morning to adjust the rhythm. For subjects evaluated to have weak stimulus protection, treatments to enhance stimulus protection can be proposed. Examples of such treatment include cosmetics having an antioxidant effect, a diet rich in polyphenols and vitamin C, slow jog that enhances the defense power of the whole body, and bathing in lukewarm water. For subjects who are evaluated as having weak damage control power, it is possible to propose measures to enhance damage control power. Such treatments include the use of anti-inflammatory cosmetics, products containing turmeric, a nutritionally balanced diet, and 10-minute exercises to prevent systemic muscle weakness. For subjects evaluated to have weak aquavitamin utilization, treatments to enhance aquavitamin utilization can be proposed. Such treatments include cosmetics and supplements containing vitamin derivatives, pork dishes, how to prepare and monitor autonomic nerves, and effective vitamin intake methods after exercise. And for subjects evaluated to have weak oil-vitamin utilization, treatments to enhance oil-vitamin utilization can be proposed. Such treatments include β-carotene supplements and fruits, diets that utilize fish and mushrooms, proper sunbathing methods, and suggestions for goods that avoid pollinosis and air pollution.

All documents referred to herein are incorporated herein by reference in their entirety.

The examples of the present invention described below are for illustration purposes only and do not limit the technical scope of the present invention. The technical scope of the invention is limited only by the description of the claims. Modifications of the present invention, for example, addition, deletion and replacement of the constituent elements of the present invention may be made on condition that the gist of the present invention is not deviated.

Example 1: Analysis target Female volunteers (1448) aged 20 to 79 years were targeted. Prior to the analysis, a questionnaire survey was conducted on age, height, weight, BMI (calculated from height and weight according to a standard method), UV exposure information, and smoking information. Regarding exposure information to UV rays, the current tanning consciousness is classified into 4 stages (2 stages of sunburn-oriented, 2 stages of non-tanning-oriented), and in order to grasp the response to UV rays in detail, from birth to the present ( 3 levels of sunburn measures (1-14 years old, 15-19 years old, 20-24 years old, 25-29 years old, and beyond in 10-year increments) (actively without UV protection, UV protection against strong sunlight) , Weak sunlight was also classified by UV protection) and the survey was conducted. The survey was divided into three groups: no smoking history, 20 or more cigarettes per day in the past, and less than 20 cigarettes per day in the past.

Example 2: Acquisition of actual skin measurement data in the analysis target As skin characteristic values, wrinkles, stains, and skin colors (cheek melanin amount, brightness, yellowness, inside upper arm) of female volunteers aged 20 to 79 years were targeted. Skin color) and elasticity were measured. For each measurement, using Visia Evolution (manufactured by Canfield Scientific) for the wrinkle state and the spot state, the index value of wrinkles and spots (spot 1) is calculated from the captured image by a dedicated analysis method, and the spot is the skin. The number of stains (stain 2) and the area of stains (stain 3) by the image measuring device were also calculated and used for the analysis. The skin color was analyzed using a spectrophotometer CM-700d (Konica Minolta), and the amount of melanin in the cheeks (skin color 1), brightness (L * / color measurement value) (skin color 2), and yellowness (b *). -Measurement value) (skin color 3) was measured, and the inner skin color of the upper arm (skin color 4) was also measured. The elasticity was measured using a dedicated commercially available device (Cutometer). For wrinkles on the eyes, a replica of the skin surface is made from silicon, three-dimensionally measured, the data is taken into a computer, and image processing is performed using a unique analysis system to calculate the maximum depth, volume, and area of the wrinkles. bottom.

Example 3: Determination of SNP in the analysis target The following 79 types of SNPs that are expected to affect the skin characteristic values were selected from the past dermatological findings.
rs1800629, rs2108622, rs1047781, rs12203592, rs16891982, rs3760776, rs9340799, rs12913832, rs17822931, rs964184, rs1801133, rs2228479, rs10515552, rs10741657, rs10882272, rs11057830, rs11234027, rs12272004, rs12377462 rs2227564, rs2282679, rs2298585, rs3829251, rs41281112, rs4654748, rs492602, rs602662, rs1030868, rs1126643, rs1256062, rs12934922, rs1485766, rs1501299, rs17577, rs1799724, rs1800012, rs1800414, rs2010963, rs2234693 rs3918242, rs4065, rs4252125, rs6152, rs7201, rs74653330, rs7501331, rs8110862, rs8326, rs833061, rs1050565, rs1799750, rs4880, rs1050450, rs6058017, rs1061622, rs2046571, rs2232228, rs3785079, rs2246416. rs3865188, rs6810075, rs7799039, rs1137101.
The selection criteria were epidermis, basement membrane, dermis, panniculus adipos, factors that function in the whole body (hormones, vitamins, etc.), enzymes, extracellular matrix proteins, etc., and genes with SNP were selected as candidates. .. It is possible that these SNPs affect various skin traits.
Next, for each of the above 79 types of SNPs, 4 types of genetic models consisting of a recessive model, a dominant model, an additive model, and a synergistic model are set, and for 79 types of SNPs, a total of 316 types of genetic models are considered. Was used as genetic information. By using this genetic information and environmental information as explanatory variables and performing variable selection using Elastic Net, the optimal genetic model for each SNP was determined. By determining the genetic model prior to the creation of the learning model according to the present invention, it is expected that the accuracy of determining the skin constitution by SNP will be improved.

Saliva was used as a sample in determining the SNP in the analysis target. Saliva was collected using Oragene® DNA OG-500 (DNA Genotek Inc.) to stabilize the DNA. DNA was purified from saliva, SNPs were determined using a DNA array, and information on the above 79 types of SNPs selected in advance was obtained.

Example 4: Creation of a learning model for classifying into a high-value group and a non-high-value group (or a low-value group and a non-low-value group) and determining the skin constitution using the classification result as an objective variable Wrinkles and stains (stains 1 to 3) ), Cheek melanin amount (skin color 1), brightness (skin color 2), yellowness (skin color 3), upper arm inner skin color (skin color 4), elasticity, wrinkle area, wrinkle volume, wrinkle maximum depth Based on the measured values of the skin condition, the high value group and the low value group of the skin condition were determined for each age group from the distribution of the respective measured values. Specifically, in the case of a high-value group model that determines the susceptibility to skin constitution (for example, if the target skin constitution is blemishes, the susceptibility to spots), the measured value of the skin obtained by the skin inspection. Is defined as 1 when it is the top 25% of all data included in each age group (range of 5 years division of age), and 0 when it is not (non-high value group) (Fig. 3). In addition, in the case of a low-value group model that determines the difficulty of skin constitution (for example, if the target skin constitution is spots, the difficulty of spots), the measured values of the skin obtained by the skin test are each. The case where it is the lower 25% of all the data included in the age (range of 5 years division of age) is defined as 1, and the other cases are defined as 0.

In the case of the high price group judgment model, the high price group is set to 1 and the non-high price group is set to 0, and information on 79 types of SNPs and information on environmental factors based on the questionnaire results are input as explanatory variables, and logistic regression analysis is performed. To create a learning model for determining the skin constitution. The number n of SNPs used in creating the learning model was set. It was prepared with n = 1 to 4 (m1) and 5 to 10 (m2), respectively. In the learning model for determining the skin constitution, a constant term is determined for each explanatory variable, and by inputting the explanatory variable, the tendency of the skin constitution to become the objective variable (possibility of belonging to the high value group of the skin condition) and / Or it is possible to output the difficulty of skin constitution (possibility of belonging to the low value group of skin condition).

Example 5: Verification of learning model For the created learning model for determining the skin constitution, the ease (or difficulty) of the skin constitution output by inputting the explanatory variables of the verification data and the verification. Based on the classification of the data into the high value group (or low value group) of the skin condition, the ROC curve was obtained, and the area under the ROC curve (AUC) and the sensitivity (Sensitivity) were obtained (FIG. 4). Sensitivity is a value set regardless of the optimum cutoff value obtained from the ROC curve (value at the point where the distance from the upper left corner of the ROC curve (point where both sensitivity and specificity are 1) is the minimum, etc.) and the ROC curve. (For example, since the skin constitution score obtained from the prediction model is a probability value, the cutoff value is set to 0.5, etc.) was used. In the learning model that determines the 100 types of skin constitution created in this way, the appearance frequency of SNP is investigated, and each skin constitution (stain 1, stain 2, stain 3, skin color 1, skin color 2, skin color 3, skin color 4, wrinkles, The table below shows the SNPs used in the learning model for determining elasticity, wrinkle area, wrinkle volume, and maximum wrinkle depth. Based on the frequency of appearance of SNPs and biochemical knowledge, the SNPs used for the learning model were selected, and from the created learning models, a learning model with a high AUC was selected while using the SNPs.

The SNPs listed above are the SNPs used in the aging model formula for each skin condition, respectively. The functional aspects of the genes to which these SNPs belong were examined, and the genes involved in skin aging resistance were confirmed. Then, SNPs that affect the function of each gene were investigated, selected, and shown in the table.

From the above SNPs, in particular the following SNPs were used for the evaluation of aging resistance:

Example 6: Evaluation of skin aging resistance Obtaining SNP information acquired from a subject, cell active power, skin shielding power, face shape modeling power, metabolism maintenance power, skin color assist power, stimulation protection power, damage control power, Scores were calculated for each of the aqua vitamin utilization ability and the oil vitamin utilization ability based on the phenotype and genetic model of each SNP. Specifically, scores were given for each SNP phenotype according to the table below. Three resistances with low scores were selected, and the three resistances recommended for the subject to prevent and strengthen the resistance. Preventive measures against aging can be proposed for the three low-scoring resistances.

Example 7 Verification of evaluated skin resistance Three types of skin aging resistance that we recommend customers to prevent and strengthen by clarifying the strength and balance of nine types of skin resistance to aging from the results of genetic tests. We have developed an algorithm to propose power. The effectiveness of this algorithm was verified based on the genetic test results, skin measurement results, and skin trouble questionnaire results of the subjects (about 1500 persons). Specifically, for the SNPs possessed by the subjects, the resistance of each skin of the subjects to aging was scored according to the definitions in Tables 25 and 26. In addition, when the three powers cannot be defined only by the genetic test results, we succeeded in narrowing down the resistance to skin aging by using the results of nine kinds of skin trouble questionnaires originally created by the present inventors. As an example, we determined the resistance score for each aging for all subjects and confirmed the distribution of the resistance score for each aging. It was confirmed that the power determination rate was 83.3% on average. As a result, this algorithm newly developed by the present inventors supports the improvement of the balance of resistance to skin aging according to the customer's personalized skin constitution and skin troubles, and is the core of the service newly developed by us. It shows that it is appropriate as a technology.

Example 8: Example showing the effectiveness of the method for determining the resistance to skin aging of the present invention Two females in their 60s, A1 and A2, who were determined to have low aquavitamin utilization (aquavitamin utilization: 1). The daily intake of water-soluble vitamins is shown in Table 27. Table 28 shows the degree of stains on both sides. Subjects with higher intake of water-soluble vitamins have less stains. This shows the effectiveness of the method for determining the resistance of the present invention, and is an example in which the influence of skin aging due to SNP is reduced by living according to the resistance.

Claims (35)

1. A method for determining skin aging resistance based on SNPs in genes involved in skin aging resistance.
2. The method according to claim 1, wherein the aging of the skin is selected from aging caused by lifestyle, aging caused by the external environment, and natural aging caused by aging.
3. The resistance to aging of the skin consists of cell active power, skin shielding power, face shape modeling power, metabolism maintenance power, skin color assist power, stimulus protection power, damage control power, aqua vitamin utilization power, and oil vitamin utilization power. The method of claim 1 or 2, wherein the method is at least one selected from the group.
4. The method of claim 2 or 3, wherein the cell active force is determined based on the SNP in at least one gene selected from the group consisting of BLMH, CASP14, and HAS3.
5. As the resistance to the aging of the skin, the following:
   At least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862 determines the resistance to skin aging for cell activity. The method according to claim 4.
6. The method according to claim 2 or 3, wherein the skin shielding force is determined based on the SNP in at least one gene selected from the group consisting of PLAU (uPA) and CASP14.
7. As the resistance to the aging of the skin, the following:
   6. Claim 6, wherein at least one SNP selected from the group consisting of rs2158467, rs2227564, rs2227566, rs2227568, rs2227574, rs3181162, rs4065, rs717309, and rs8110862 determines the resistance to skin aging with respect to skin shielding power. the method of.
8. Face shape modeling power is determined based on SNPs in at least one gene selected from the group consisting of MMP-1, MMP-2, MMP-9, ELN, HAS2, FBRN5, and COL1A1. The method according to 3.
9. As the resistance to the aging of the skin, the following:
   rs1799750, rs10233395, rs1030868, rs1057297, rs1057308, rs1061237, rs1061947, rs1107946, rs1144391, rs13925, rs13969, rs17576, rs17577, rs17804735, rs17855988, rs17884110, rs1800012, rs1871884, rs2046571 Claim that at least one SNP selected from the group consisting of rs2856728, rs4255143, rs4618701, rs470558, rs5854, rs7149187, rs7201, rs77357345, rs8326, and rs9509 determines the resistance to skin aging with respect to facial shape modeling ability. 8. The method according to 8.
10. The method according to claim 2 or 3, wherein the metabolic maintenance ability is determined based on SNP in at least one gene selected from the group consisting of VEGFA and VEGFC.
11. As the resistance to the aging of the skin, the following:
    10. The claim 10, wherein at least one SNP selected from the group consisting of rs1485766, rs10434, rs2010963, rs475106, rs475920, rs510684, rs699947, rs735286, and rs833061 determines the resistance of skin to aging with respect to metabolic maintenance. the method of.
12. The method according to claim 2 or 3, wherein the skin color assisting force is determined based on SNP in at least one gene selected from the group consisting of OCA2 and IRF4.
13. As the resistance to the aging of the skin, the following:
    Claim 12 that at least one SNP selected from the group consisting of rs1800414, rs1050975, rs1131442, rs12203592, rs12913832, rs1540771, rs1800404, rs1800411, rs74653330, and rs872071 determines the resistance to skin aging with respect to skin color assist. The method described in.
14. The method according to claim 2 or 3, wherein the stimulus protection force is determined based on the SNP in at least one gene selected from the group consisting of SOD2 and GPX1.
15. As the resistance to the aging of the skin, the following:
    14. The method described in.
16. The method according to claim 2 or 3, wherein the damage control force is determined based on SNP in at least one gene selected from the group consisting of TNF-α, PLAU (uPA), and TNFR2.
17. As the resistance to the aging of the skin, the following:
    At least one SNP selected from the group consisting of rs1799724, rs1061622, rs1800629, rs2227564, rs2227566, rs2227568, rs2227574, rs235249, rs3093662, rs3397, rs361525, rs4065, rs472093, rs474247, and rs673 for damage control against skin aging. 16. The method of claim 16, wherein the resistance is determined.
18. The method according to claim 2 or 3, wherein the aquavitamin utilization ability is determined based on SNP in at least one gene selected from the group consisting of genes related to the control of vitamin B2 level and vitamin B12 level in blood.
19. As the resistance to the aging of the skin, the following:
    18. The method of claim 18, wherein at least one SNP selected from the group consisting of rs1801133, rs1047781, rs10515552, rs2298585, and rs3760776 determines the resistance to skin aging with respect to aquavitamin utilization.
20. Oil Vitamin utilization is determined based on SNP in at least one gene selected from the group consisting of genes related to control of vitamin A level, vitamin D level, and vitamin E level in blood, claim 2 or 3. The method described in.
21. As the resistance to the aging of the skin, the following:
    At least one SNP selected from the group consisting of rs10882272, rs11057830, rs11234027, rs12272004, rs12785878, rs12934922, rs1667255, rs1993116, rs2060793, rs2108622, rs2282679, rs7501331 and rs964184 provides resistance to skin aging for oil vitamin utilization. The method of claim 20, as determined.
22. A method of proposing preventive measures against aging according to the resistance determined by the method according to any one of claims 1 to 21.
23. Multiple resistances selected from the group consisting of cell active power, skin shielding power, face shape modeling power, metabolism maintenance power, skin color assist power, stimulation protection power, damage control power, aqua vitamin utilization power, and oil vitamin utilization power 22. The method of claim 22, wherein a corresponding preventive action is proposed for at least one resistance that has been determined and determined to be low resistance.
24. It is a device that determines the resistance of the skin to aging.
    Input section for inputting SNP information about genes involved in skin aging resistance,
    A storage unit that stores the relationship between SNP information and the resistance of the skin to aging in advance.
    A processing unit that compares the relationship between the SNP information input from the input unit, the SNP information stored in advance in the storage unit, and the resistance to skin aging, and determines the resistance to skin aging.
    The determination device comprising an output unit that outputs a determined resistance to skin aging.
25. The resistance to aging of the skin consists of cell active power, skin shielding power, face shape modeling power, metabolism maintenance power, skin color assist power, stimulus protection power, damage control power, aqua vitamin utilization power, and oil vitamin utilization power. The determination device according to claim 24, which is at least one selected from the group.
26. The gene involved in cell active force is at least one gene selected from the group consisting of BLMH, CASP14, and HAS3.
    The gene involved in the skin shielding force is at least one gene selected from the group consisting of PLAU (uPA) and CASP14.
    The gene involved in face shape modeling ability is at least one gene selected from the group consisting of MMP-1, MMP-2, MMP-9, ELN, HAS2, FBRN5, and COL1A1.
    The gene involved in metabolic maintenance is at least one gene selected from the group consisting of VEGFA and VEGFC.
    The gene involved in skin color assisting power is at least one gene selected from the group consisting of OCA2 and IRF4.
    The gene involved in stimulus protection is at least one gene selected from the group consisting of SOD2 and GPX1.
    The gene involved in damage control is at least one gene selected from the group consisting of TNF-α, PLAU (uPA), and TNFR2.
    The gene involved in aquavitamin utilization is at least one gene selected from the group consisting of genes related to the control of vitamin B2 level and vitamin B12 level in blood.
    The determination according to claim 25, wherein the gene involved in the ability to utilize oil vitamins is at least one gene selected from the group consisting of genes related to the control of vitamin A level, vitamin D level, and vitamin E level in blood. Device.
27. SNP information about genes involved in cell active force is as follows:
    Information about at least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862.
    SNP information about genes involved in skin shielding is as follows:
    Information about at least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862.
    SNP information about genes involved in face shape modeling ability is as follows:
    rs1799750, rs10233395, rs1030868, rs1057297, rs1057308, rs1061237, rs1061947, rs1107946, rs1144391, rs13925, rs13969, rs17576, rs17577, rs17804735, rs17855988, rs17884110, rs1800012, rs1871884, rs2046571 Information about at least one SNP selected from the group consisting of rs2856728, rs4255143, rs4618701, rs470558, rs5854, rs7149187, rs7201, rs77357345, rs8326, and rs9509.
    SNP information about genes involved in metabolic maintenance is as follows:
    Information about at least one SNP selected from the group consisting of rs1485766, rs10434, rs2010963, rs475106, rs475920, rs510684, rs699947, rs735286, and rs833061.
    SNP information about genes involved in skin color assisting power is as follows:
    At least one SNP selected from the group consisting of rs1800414, rs1050975, rs1131442, rs12203592, rs12913832, rs1540771, rs1800404, rs1800411, rs74653330, and rs872071.
    Information about
    SNP information about genes involved in stimulus protection is as follows:
    Information about at least one SNP selected from the group consisting of rs4880, rs10370, rs1050450, rs1800668, rs3448, rs3811699, rs732498, rs7855, rs8031 and rs8179164.
    SNP information about genes involved in damage control is as follows:
    Information about at least one SNP selected from the group consisting of rs1799724, rs1061622, rs1800629, rs2227564, rs2227566, rs2227568, rs2227574, rs235249, rs3093662, rs3397, rs361525, rs4065, rs472093, rs474247, and rs673.
    SNP information on genes involved in aquavitamin utilization is as follows:
    Information about at least one SNP selected from the group consisting of rs1801133, rs1047781, rs10515552, rs2298585, and rs3760776.
    SNP information on genes involved in oil-vitamin utilization is as follows:
    25 or 26, which is information about at least one SNP selected from the group consisting of rs10882272, rs11057830, rs11234027, rs12272004, rs12785878, rs12934922, rs1667255, rs1993116, rs2060793, rs2108622, rs2282679, rs7501331 and rs964184. Determining device.
28. The memory unit further memorizes preventive measures according to the resistance of the skin to aging.
    The processing unit reads out the preventive measures according to the resistance determined in the processing unit from the storage unit.
    The determination device according to any one of claims 24 to 27, wherein the output unit outputs the read preventive action.
29. The determination device is selected from the group consisting of cell active power, skin shielding power, face shape modeling power, metabolism maintenance power, skin color assisting power, stimulus protection power, damage control power, aquavitamin utilization power, and oil vitamin utilization power. 28. The determination device according to claim 28, wherein a plurality of resistance forces are determined, and the output unit of the determination device outputs a corresponding preventive measure for at least one resistance force determined to have a low resistance force.
30. A program that allows a computer, including an input unit, a storage unit, a processing unit, and an output unit, to determine the resistance to skin aging, and is described below.
    Skin based on the relationship between the SNP information about the genes involved in the resistance to skin aging input from the input unit to the processing unit, the pre-SNP information stored in the storage unit in advance, and the resistance to skin aging. Command to determine resistance to aging;
    The program comprising a command to output the determined resistance to skin aging from the output unit.
31. The resistance to aging of the skin consists of cell active power, skin shielding power, face shape modeling power, metabolism maintenance power, skin color assist power, stimulus protection power, damage control power, aqua vitamin utilization power, and oil vitamin utilization power. 30. The program of claim 30, wherein the program is at least one selected from the group.
32. The gene involved in cell active force is at least one gene selected from the group consisting of BLMH, CASP14, and HAS3.
    The gene involved in the skin shielding force is at least one gene selected from the group consisting of PLAU (uPA) and CASP14.
    The gene involved in face shape modeling ability is at least one gene selected from the group consisting of MMP-1, MMP-2, MMP-9, ELN, HAS2, FBRN5, and COL1A1.
    The gene involved in metabolic maintenance is at least one gene selected from the group consisting of VEGFA and VEGFC.
    The gene involved in skin color assisting power is at least one gene selected from the group consisting of OCA2 and IRF4.
    The gene involved in stimulus protection is at least one gene selected from the group consisting of SOD2 and GPX1.
    The gene involved in damage control is at least one gene selected from the group consisting of TNF-α, PLAU (uPA), and TNFR2.
    The gene involved in aquavitamin utilization is at least one gene selected from the group consisting of genes related to the control of vitamin B2 level and vitamin B12 level in blood.
    The gene according to claim 31, wherein the gene involved in the oil-vitamin utilization is at least one gene selected from the group consisting of genes related to the control of vitamin A level, vitamin D level, and vitamin E level in blood. program.
33. SNP information about genes involved in cell active force is as follows:
    Information about at least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862.
    SNP information about genes involved in skin shielding is as follows:
    Information about at least one SNP selected from the group consisting of rs1050565, rs1552472, rs2129785, rs2158467, rs2232227, rs2232228, rs3103308, rs3181162, rs3190884, rs3759981, rs3785079, rs717309, and rs8110862.
    SNP information about genes involved in face shape modeling ability is as follows:
    rs1799750, rs10233395, rs1030868, rs1057297, rs1057308, rs1061237, rs1061947, rs1107946, rs1144391, rs13925, rs13969, rs17576, rs17577, rs17804735, rs17855988, rs17884110, rs1800012, rs1871884, rs2046571 Information about at least one SNP selected from the group consisting of rs2856728, rs4255143, rs4618701, rs470558, rs5854, rs7149187, rs7201, rs77357345, rs8326, and rs9509.
    SNP information about genes involved in metabolic maintenance is as follows:
    Information about at least one SNP selected from the group consisting of rs1485766, rs10434, rs2010963, rs475106, rs475920, rs510684, rs699947, rs735286, and rs833061.
    SNP information about genes involved in skin color assisting power is as follows:
    At least one SNP selected from the group consisting of rs1800414, rs1050975, rs1131442, rs12203592, rs12913832, rs1540771, rs1800404, rs1800411, rs74653330, and rs872071.
    Information about
    SNP information about genes involved in stimulus protection is as follows:
    Information about at least one SNP selected from the group consisting of rs4880, rs10370, rs1050450, rs1800668, rs3448, rs3811699, rs732498, rs7855, rs8031 and rs8179164.
    SNP information about genes involved in damage control is as follows:
    Information about at least one SNP selected from the group consisting of rs1799724, rs1061622, rs1800629, rs2227564, rs2227566, rs2227568, rs2227574, rs235249, rs3093662, rs3397, rs361525, rs4065, rs472093, rs474247, and rs673.
    SNP information on genes involved in aquavitamin utilization is as follows:
    Information about at least one SNP selected from the group consisting of rs1801133, rs1047781, rs10515552, rs2298585, and rs3760776.
    SNP information on genes involved in oil-vitamin utilization is as follows:
    31 or 32, which is information about at least one SNP selected from the group consisting of rs10882272, rs11057830, rs11234027, rs12272004, rs12785878, rs12934922, rs1667255, rs1993116, rs2060793, rs2108622, rs2282679, rs7501331 and rs964184. program.
34. The program is as follows:
    A command to memorize the treatment according to the resistance of the skin to aging in the storage part,
    A command to operate the processing unit to read the treatment according to the resistance determined in the processing unit from the storage unit,
    The program according to any one of claims 30 to 33, further comprising a command to output the read action to the output unit.
35. The above program is selected from the group consisting of cell active power, skin shielding power, face shape modeling power, metabolism maintenance power, skin color assist power, stimulus protection power, damage control power, aqua vitamin utilization power, and oil vitamin utilization power in the computer. A command to determine multiple resistances,
    34. The program of claim 34, comprising a command to output a corresponding preventive action for at least one resistance determined by the processing unit to be low resistance.

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