JP7082834B1 - How to determine the genetic predisposition to the tendency of the face to turn red - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a means for accurately and easily determining a genetic predisposition for a person's face to become red easily. SOLUTION: This is a step of detecting a single nucleotide polymorphism (SNP) identified by rs11065950, rs11066001, rs144504271 or an allele of SNP having a linkage disequilibrium relationship with these SNPs in a DNA-containing sample collected from a subject. The genetic predisposition to redness of the face, comprising the step of determining that the subject has a genetic predisposition to redness of the face when at least one of the detected allele bases is a risk allele. How to judge. [Selection diagram] None

Description

The present invention relates to a method for determining a genetic predisposition to the tendency of a face to turn red. More specifically, the present invention relates to a method for determining a genetic predisposition to facial redness by detecting a single nucleotide polymorphism (SNP) associated with facial redness, and a kit used for the method.

The color of the skin is regulated by melanin, hemoglobin, carotene, etc., and exhibits various colors such as redness and yellowness in addition to the basic white to black. This does not always maintain a constant color tone, but continues to fluctuate due to external factors such as ultraviolet rays and the effects of mental and physical changes such as aging. Among these, it is known that the redness of the skin changes in various situations such as changes in temperature, tension, excitement, and exercise. Moderately reddish skin is ruddy and gives a healthy and lively impression, so blush may be used to obtain such an appearance. On the other hand, rosacea and the like are examples of skin diseases in which the face becomes chronically red. Rosacea is a chronic inflammatory disease characterized by flushing of the face, telangiectasia, etc., and is thought to be caused by abnormal vasomotor control and hormonal balance, ticks in hair follicles, and increased active oxygen. However, the details have not been clarified.

So far, genes suggested to be associated with alcohol scabs and telangiectasia and methods for predicting the risk of developing diseases using single nucleotide polymorphisms (SNPs) as indicators have been known (Non-Patent Document 1). 2). However, the search for genes and SNPs that can predict the tendency of temporary facial redness when changes occur in the environment such as temperature and tension and mental state has not been conducted.

Anne Lynn S Chang et al., Assessment of the Genetic Basis of Rosacea by Genome-Wide Association Study, J Invest Dermatol. 2015 Jun; 135 (6): 1548-1555 S Mekic et al., Genetics of facial telangiectasia in the Rotterdam Study: a genome-wide association study and candidate gene approach.

An object of the present invention is to provide a means for accurately and easily determining the genetic predisposition of an individual's facial redness.

As a result of diligent research to solve the above problems, the present inventors have found that rs11065950, rs11066001, rs144504271 and SNPs having a linkage disequilibrium relationship can predict the tendency of the face to turn red. The present invention has been completed.

That is, the present invention includes the following inventions.
[1] In the DNA-containing sample collected from the subject, the step of detecting one or more single nucleotide polymorphism (SNP) alleles of the following (a1) to (a6) and the base of the detected allele. A method for determining a genetic predisposition to the tendency of a face to turn red, which comprises a step of determining that the subject's face is likely to turn red when at least one of the alleles is a risk allele.
(a1) SNP at the 101st base of the base sequence shown in SEQ ID NO: 1 (SNP: SNP specified by ID rs11065950)
(a2) SNP having a linkage disequilibrium coefficient r2 ≧ 0.8 with SNP (SNP: SNP specified by ID rs11065950) at the 101st base of the base sequence shown in SEQ ID NO: 1.
(a3) SNP at the 101st base of the base sequence shown in SEQ ID NO: 5 (SNP: SNP specified by ID rs11066001)
(a4) The SNP in the 101st base of the base sequence shown in SEQ ID NO: 5 (SNP: SNP specified by ID rs11066001) and the SNP having a linkage disequilibrium coefficient r2 ≧ 0.8.
(a5) SNP at the 101st base of the base sequence shown in SEQ ID NO: 7 (SNP: SNP specified by ID rs144504271)
(a6) SNP having a linkage disequilibrium coefficient r2 ≧ 0.8 with SNP (SNP: SNP specified by ID rs144504271) at the 101st base of the base sequence shown in SEQ ID NO: 7.
[2] The SNP having a chain imbalance coefficient r2 ≧ 0.8 with the SNP (SNP: SNP specified by ID rs11065950) at the 101st base of the base sequence shown in SEQ ID NO: 1 of (a2) is a sequence. SNP at the 101st base of the base sequence shown in No. 2 (SNP: SNP specified by ID rs11065939), SNP at the 101st base of the base sequence shown in SEQ ID NO: 3 (SNP: ID rs7964109) SNP), or the method according to [1], which is an SNP (SNP: SNP specified by ID rs3815021) at the 101st base of the base sequence shown in SEQ ID NO: 4.
[3] The SNP having a linkage disequilibrium coefficient r2 ≧ 0.8 with the SNP (SNP: SNP specified by ID rs11066001) at the 101st base of the base sequence shown in SEQ ID NO: 5 of (a4) is a sequence. The method according to [1], which is an SNP (SNP: SNP specified by ID rs3782886) at the 101st base of the base sequence shown in No. 6.
[4] The SNP having a linkage disequilibrium coefficient r2 ≧ 0.8 with the SNP (SNP: SNP specified by ID rs144504271) at the 101st base of the base sequence shown in SEQ ID NO: 7 of (a6) is a sequence. The method according to [1], which is an SNP (SNP: SNP specified by ID rs2074356) at the 101st base of the base sequence shown in No. 8.
[5] Based on the results determined by the method according to any one of [1] to [4], cosmetics and / or foods and drinks according to the degree of genetic predisposition to the subject's facial redness. A method of providing cosmetics and / or foods and drinks, which is provided to the subject.
[6] A cosmetology counseling method according to the degree of genetic predisposition to the tendency of the subject's face to turn red based on the result determined by the method according to any one of [1] to [4].
[7] SNP (SNP: SNP specified by ID rs11065950) at the 101st base of the base sequence shown in SEQ ID NO: 1 and SNP (SNP: ID rs11066001) at the 101st base of the base sequence shown in SEQ ID NO: 5. SNP specified in), SNP at the 101st base of the base sequence shown in SEQ ID NO: 7 (SNP: SNP specified by ID rs144504271), or SNP having a chain imbalance coefficient r2 ≧ 0.8 with the SNP. SNP (SNP: SNP specified by ID rs11065950), SEQ ID NO: 5 at the 101st base of the base sequence shown in SEQ ID NO: 1 and / or a probe having a sequence containing 10 or more bases or a complementary sequence thereof. SNP at the 101st base of the base sequence shown in (SNP: SNP specified by ID rs11066001), SNP at the 101st base of the base sequence shown in SEQ ID NO: 7 (SNP: SNP specified by ID rs144504271) Or, a kit for determining the genetic predisposition to redness of the face, which comprises a primer capable of amplifying a region containing an SNP having a chain imbalance coefficient r2 ≧ 0.8 with the SNP.

According to the method of the present invention, by detecting a single nucleotide polymorphism (SNP) allele contained in genome-derived DNA present in a biological sample of a subject, the tendency of the subject to turn red on the face can be accurately and easily determined. Can be determined. Therefore, based on this determination result, it is possible to make correct selection of cosmetics and foods and drinks and beauty advice according to the degree of susceptibility to redness of the face. In addition, measures can be taken at an early stage to prevent or improve flushing of the face.

1. 1. Method for determining the genetic predisposition of facial redness The method for determining the genetic predisposition of facial redness of the present invention is a specific single nucleotide related to the genetic predisposition of an individual's facial redness. A polymorphism (SNP) or an SNP that is in linkage disequilibrium with the SNP is used to predict the tendency of the face to turn red. In the present invention, "easiness of redness of the face" means temperature difference, tension, excitement, emotions (embarrassment, anger, etc.), work under the scorching sun, hot flashes during menopause (hot flashes, hot flashes), and hormonal imbalance. , Sweat during exercise, fever, erroneous skin care such as excessive rubbing due to face washing and massage, etc., due to factors other than drinking, it means that the face tends to become red (flushing) mainly on the cheeks and forehead.

The above-mentioned "linkage disequilibrium" means that two alleles are linked to each other more frequently than when they are inherited independently. A group of alleles exhibiting such linkage disequilibrium is called a haplotype. In the present invention, an SNP having a linkage disequilibrium coefficient r2 of 0.8 or more, preferably 0.9 or more, more preferably 0.95 or more, and most preferably 1 can be used. SNPs that are in linkage disequilibrium with a particular SNP include, for example, the Ensembl Genome Browser (https://asia.ensembl.org/index.html) and the HapMap database (http://www.hapmap.org/index.html. It can be identified using ja) and the like. Alternatively, DNA collected from a plurality of people (usually about 20 to 40 people) can be identified by sequence analysis with a sequencer and searching for SNPs having linkage disequilibrium.

The method for determining the genetic predisposition to redness of the face of the present invention is to determine one or more single nucleotide polymorphisms (SNP) of the following (a1) to (a6) in a DNA-containing sample collected from a subject. ) Includes a step of detecting the allele and a step of determining that the subject's face is likely to turn red when at least one of the detected allele bases is a risk allele.
(a1) SNP at the 101st base of the base sequence shown in SEQ ID NO: 1 (SNP: SNP specified by ID rs11065950)
(a2) SNP having a linkage disequilibrium coefficient r2 ≧ 0.8 with SNP (SNP: SNP specified by ID rs11065950) at the 101st base of the base sequence shown in SEQ ID NO: 1.
(a3) SNP at the 101st base of the base sequence shown in SEQ ID NO: 5 (SNP: SNP specified by ID rs11066001)
(a4) The SNP in the 101st base of the base sequence shown in SEQ ID NO: 5 (SNP: SNP specified by ID rs11066001) and the SNP having a linkage disequilibrium coefficient r2 ≧ 0.8.
(a5) SNP at the 101st base of the base sequence shown in SEQ ID NO: 7 (SNP: SNP specified by ID rs144504271)
(a6) SNP having a linkage disequilibrium coefficient r2 ≧ 0.8 with SNP (SNP: SNP specified by ID rs144504271) at the 101st base of the base sequence shown in SEQ ID NO: 7.

Examples of SNPs having a linkage disequilibrium coefficient r2 ≧ 0.8 with the SNP specified by rs11065950 in (a2) above include rs3858705, rs11065939, rs7969300, rs58937998, rs11065953, rs10849958, rs7964109, rs6490187, rs10774626, rs11065946, rs118002600, rs7301158. , Rs11065941, rs11065959, rs11065960, rs11065963, rs11065965, rs142096264, rs3815021 and the like.

Examples of the SNP having a linkage disequilibrium coefficient r2 ≧ 0.8 with the SNP specified by rs11066001 in (a4) above include SNPs specified by rs11066015, rs3782886, and the like.

Examples of the SNP having a linkage disequilibrium coefficient r2 ≧ 0.8 with the SNP specified by rs144504271 in (a6) above include the SNP specified by rs2074356 and the like.

Table 1 shows the SNPs associated with the redness of the face and the base sequence containing the SNPs having a linkage disequilibrium coefficient r2 ≧ 0.8 (indicated by []).

As shown in the results of the examples below, the SNPs of rs11065950, rs11065939, rs7964109, rs3815021, rs11066001, rs3782886, rs144504271, and rs2074356 have been statistically proven to be statistically associated with the genetic predisposition to redness of the face. It is a thing. Although it is possible to determine the genetic predisposition of the tendency of the face to turn red even with one of the above SNPs, it is possible to improve the determination accuracy by combining two or more types and increase the pattern of the types of determination. ..

Single nucleotide polymorphism (SNP, hereinafter may be referred to as "SNP") generally refers to a state in which the base sequence of a gene differs only at one site and its site. In addition, the polymorphism generally refers to two or more alleles (alleles) that are present at a frequency of 1% or more in the population. The "SNP" in the present invention is an SNP database (http://www.ncbi.nlm) of the National Center for Biotechnology Information (NCBI), which is a public database freely available to those skilled in the art. It is an SNP registered in .nih.gov/SNP/) and can be specified by its reference number, rs number.

As used herein, the term "allele" refers to each type having different bases that can be taken at a certain SNP site. Further, as used herein, the term "genotype" refers to a combination of alleles that oppose each other at a certain SNP site. At a certain SNP site, there are three types of genotypes that are the combination, the combination of the same allele is called the homozygous type, and the combination of different alleles is called the heterozygous type. For example, there are three types of genotypes, C / C type, C / A type, and A / A type, which are combinations of alleles that conflict with each other in SNP identified by rs11065950.

In the determination method of the present invention, "detecting a single nucleotide polymorphism (SNP) allele" means identifying the type of base of the SNP allele, and "single nucleotide polymorphism (SNP) allele". The aspect of "detecting" includes detecting one allele of the SNP, detecting both alleles of the SNP, and identifying the genotype of the SNP.

In the determination method of the present invention, when at least one of the detected allele bases is a risk allele, it is determined that the subject has a genetic predisposition to make the face red. For example, in rs11065939, rs7964109, rs3815021, which are SNPs having a linkage disequilibrium coefficient r2 ≥ 0.8 with rs11065950 or rs11065950, in rs3782886, which is an SNP having a linkage disequilibrium coefficient r2 ≥ 0.8 with rs11066001 or rs11066001, or. In rs2074356, which is an SNP having a linkage disequilibrium coefficient r2 ≧ 0.8 with rs144504271 or rs144504271, if the risk allele shown in Table 2 below is detected in at least one of the alleles, it is compared with the case where the risk allele is not detected. Therefore, it can be determined that the skin tends to become red. On the contrary, when the risk allele is not detected, it can be determined that the skin is less likely to become red than when the risk allele is detected.

For example, in the case of SNPs identified by rs11065950, the genotype of C / C indicates that the face is more likely to turn red than the C / A or A / A types, and the genotype is inherited. The fact that the type is C / A indicates that the face is more likely to be red than the case of A / A type. That is, it is shown that the face tends to turn red in the order of C / C type, C / A type, and A / A type. In other words, it shows that the face is less likely to turn red in the order of A / A type, C / A type, and C / C type.

In the determination method of the present invention, the race of the subject is not particularly limited, but is preferably East Asian, more preferably Japanese. Here, the East Asian means a person whose origin is any of the people of Japan, Korea, China, Taiwan and Mongolia.

The DNA-containing sample used in the determination method of the present invention is not particularly limited as long as it is a biological sample containing DNA collected from a subject. The DNA contained in the DNA-containing sample is preferably genomic DNA, but the detected SNP is located in a region existing in mRNA other than a non-transcription region such as a promoter or a region excluded by RNA splicing such as an intron. In the case of a localized SNP, a biological sample containing mRNA or total RNA may be used instead of genomic DNA. As the DNA-containing sample, for example, any body fluid, secretory fluid, tissue, cell, tissue or cell culture from which genomic DNA can be collected can be used, and specifically, saliva, blood, etc. of the subject. Urine, sputum, pharyngeal swab, nasal swab, oral (inner cheek) mucosal swab, lacrimal gland secretion, sweat, hair, nails, skin, mucous membrane, tape strip peeled off after skin adhesion, etc. Saliva is preferred because of its minimal invasiveness. The sample can be collected according to a method performed in a general clinical test, and can be prepared by using a known extraction method and purification method. At that time, a commercially available genomic DNA extraction kit can be used.

The method for detecting SNPs and determining the type of SNPs (SNP typing) is not particularly limited, and for example, allele-specific primers (and probes) are used, amplified by the PCR method, etc., and the polymorphism of the amplified product is fluorescent or luminescent. It can be carried out by a known method such as a method of detecting by. For example, PCR-RFLP (restriction fragment length polymorphism) method, PCR-SSCP (single-strand conformation polymorphism) method, PCR-SSO (sequence specific oligonucleotide) method, direct sequencing method, ASO (Allele Specific Oligonucleotide) high Hybridization method, ASP-PCR (Allele Specific Primer-PCR) method, Snapshot method, ARMS (Amplification Refracting Mutation System) method, TaqMan PCR method, Invader method, MALDI-TOF / MS method, RNase A cleavage method, DOL (Dye-) Labeled Oligonucleotide Ligation) method, TDI (Template-directed Dye-terminator Incorporation) and the like can be mentioned. All of the above methods are well known to those skilled in the art, and reagents and kits for determining the type of SNP are also commercially available. For example, TaqMan SNP Genotyping Assays (manufactured by Thermo Fisher Scientific) may be used. Can be done.

The result obtained by the above-mentioned determination method is a useful index for the subject to select a cosmetic and / or a food or drink according to the degree of susceptibility to redness of the face. For example, for a subject who is determined to have a genetic predisposition that makes the face less likely to turn red, it is possible to recommend measures to make the face look better and / or promote blood circulation, while a genetic predisposition that makes the face more likely to turn red. Measures to prevent and / or improve facial flushing can be recommended for subjects who are determined to have hot flashes. Therefore, according to another aspect of the present invention, based on the results obtained by the above-mentioned determination method, cosmetics and / or foods and drinks according to the degree of genetic predisposition of the subject's face to be reddened are provided. Based on the method of providing cosmetics and / or foods and drinks provided to the subject and the results obtained by the above-mentioned determination method, cosmetology according to the degree of genetic predisposition of the subject's face to be reddened easily. Counseling methods are also provided. Specifically, as measures to make the complexion of the face look good and / or to promote blood circulation, for example, makeup base (base makeup), foundation, cheeks, lipsticks, eye shadows and other cosmetics that make the complexion look good, and blood circulation promotion It includes selection of cosmetics and / or foods and drinks containing ingredients having an action, massage method and stretching method for improving blood circulation, bathing method and the like. In addition, as measures to prevent and / or improve facial flushing, for example, a component having a makeup base (control color) covering redness, a capillary contraction action, a blood flow improving action, a barrier function promoting action, an anti-inflammatory action, and the like. Includes selection of cosmetics and / or foods and drinks containing the above, advice on not using peeling agents, scrubbing agents, etc., and correct facial washing and massage methods that do not cause excessive rubbing.

2. 2. Kit for determining the genetic predisposition of facial redness In the above-mentioned SNP detection and typing method, probes and primers corresponding to each method are used. Such probes and primers are also included in the scope of the present invention and can be provided as a kit.

Examples of the probe include the above-mentioned SNP site, and a probe capable of discriminating the type of base of the SNP site depending on the presence or absence of hybridization can be mentioned. Specifically, the SNP at the 101st base of the base sequence shown in SEQ ID NO: 1 (SNP: SNP specified by ID rs11065950) and the SNP at the 101st base of the base sequence shown in SEQ ID NO: 5 (SNP :). SNP specified by ID rs11066001), SNP at the 101st base of the base sequence shown in SEQ ID NO: 7 (SNP: SNP specified by ID rs144504271), or the relationship between the SNP and the chain imbalance coefficient r2 ≧ 0.8. Examples thereof include a probe having a sequence having 10 or more bases including a certain SNP, preferably a sequence having 15 or more bases or a complementary sequence thereof. The length of the probe is preferably 15-40 bases, more preferably 20-35 bases. The probe may be labeled with an appropriate labeling substance, and examples of the labeling substance include enzymes (peroxidase, β-galactosidase, alkaline phosphatase, etc.), fluorescent substances (FITC, RITC, Cy3, Cy5, etc.), and the like. Examples thereof include luminescent substances (luminol, luminol derivatives, luciferin, lucigenin, etc.), radioisotopes ( ³ H, ¹⁴ C, ³² P, ¹²⁵ I, ¹³¹ I, etc.), biotin, digoxigenin, polypeptides containing tag sequences, and the like. Alternatively, a quencher (quenching substance) that absorbs the fluorescent energy emitted by the fluorescent substance may be further bonded in the vicinity of the fluorescent substance.

Further, the probe may be immobilized on a solid phase (DNA array). The DNA array can simultaneously detect hybridization for each probe by hybridizing sample DNA to a large number of probes arranged on the same plane and scanning the plane. Therefore, DNA arrays are useful for simultaneously analyzing a large number of SNP sites. The oligonucleotides that serve as probes to be mounted on the array are usually synthesized in situ. For example, an in situ synthesis method of an oligonucleotide by a lithography method (Thermo Fisher Scientific), an inkjet method (Agilent), a bead array method (Illumina), or the like is known.

Examples of the primer include a primer that can be used for PCR for amplifying the SNP site, and a primer that can be used for sequence analysis (sequencing) of the SNP site. Specifically, the SNP at the 101st base of the base sequence shown in SEQ ID NO: 1 (SNP: SNP specified by ID rs11065950) and the SNP at the 101st base of the base sequence shown in SEQ ID NO: 5 (SNP :). SNP specified by ID rs11066001), SNP at the 101st base of the base sequence shown in SEQ ID NO: 7 (SNP: SNP specified by ID rs144504271), or the relationship between the SNP and the chain imbalance coefficient r2 ≧ 0.8. Examples include primers that can amplify or sequence regions containing certain SNPs. The primer that can be used for PCR for amplifying the SNP site may be an oligonucleotide that can initiate complementary strand synthesis toward the SNP site using the DNA of the region containing the SNP site as a template. The length of such a primer is preferably 10 to 30 bases, more preferably 15 to 25 bases. Primers can be set at positions upstream or downstream of the SNP site.

Those skilled in the art can design probes and primers according to the analysis method based on the base sequence information of the peripheral DNA region including the SNP site. Further, the oligonucleotide to be a probe and a primer is prepared by using a DNA automatic synthesizer usually used by a method known in the art as a method for synthesizing an oligonucleotide, for example, a phosphoramidite method, an H-phosphonate method or the like. It is possible to synthesize.

The kit of the present invention may contain at least the oligonucleotide used as the above-mentioned probe and primer. In addition, if necessary, the kit includes reagents for DNA extraction, reagents for PCR such as PCR buffers and DNA polymerases, reagents for detection such as stains and gels for electrophoresis, immobilization carriers, labeling substances, and the like. It can also include substrate compounds used to detect the label, positive and negative standard samples, instructions describing how to use the kit, and the like. The reagent in the kit may be a solution or a freeze-dried product.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, the present invention is not limited thereto.

(Example 1) Identification of a single nucleotide polymorphism (SNP) related to the genetic predisposition of facial redness. Received approval. Samples were collected from the sample donors who received consent by signing the consent form, and genotyping and related analysis were performed.

(1) DNA sample
Saliva was collected from 652 Japanese female subjects aged 21 to 50 years (mean age 40.8 years), and genomic DNA was extracted using the Maxwell RSC Stabilized Saliva DNA Kit (manufactured by Promega) to obtain DNA samples.

(2) Analyzed SNP
Among the SNPs registered in the SNP database (http://www.ncbi.nlm.nih.gov/SNP/), rs11065950, rs11066001, and rs144504271 were analyzed. Furthermore, referring to the Ensembl Genome Browser (https://asia.ensembl.org/index.html), the SNPs (linkage disequilibrium coefficient r2 ≧ 0.8) that have a linkage disequilibrium relationship with each SNP in Japanese are shown. It is shown in Table 3. Of these, rs11065939, rs7964109, rs3815021, rs3782886, and rs2074356 were also analyzed. In addition, rs763035 (Comparative Example 1), which is suggested to be associated with alcohol, and rs4417318 (Comparative Example 2), which is suggested to be associated with telangiectasia, were also analyzed as comparative examples.

(3) Genotype determination For the DNA sample obtained in (1), TaqMan SNP Genotyping Assays (manufactured by Applied Biosystems) and SsoAdvanced Universal Probes Supermix (manufactured by Bio Rad) were used in the CFX384 Touch Real-Time PCR Detection System. The genotype was determined by (Bio Rad).

(4) Phenotypic data (easiness of redness of face)
Questionnaire items regarding the tendency of the face to turn red are "1. It is difficult to turn red" and "It is difficult to turn red" in response to the question "Is the type of face that tends to turn red except when drinking alcohol? One of the three options, "Sometimes it may turn red" and "3. It tends to turn red", was answered and treated as an interval scale.

(5) Association analysis Regarding the relationship between the hereditary data and the tendency of the face to turn red, multiple regression analysis was performed with the phenotypic data as the objective variable, the number of minor alleles of the hereditary data, and the age as the explanatory variables. The p value of the partial regression coefficient of the number of minor alleles was evaluated. Since 10 types of SNPs were analyzed, the significance level was corrected by the Bonferroni method to avoid the increase of type I errors (0.05 / 10), and it was significant when the p-value was less than 0.005 (5E-03). Judged to be relevant.

(6) Results Table 4 shows the chromosome number, physical position, allele, minor allele and risk allele base, regression coefficient, and p-value of each SNP analyzed. If the sign of the regression coefficient is positive, the minor allele is the risk allele, and if the sign of the regression coefficient is negative, the major allele is the risk allele. In the p-value column, each p-value is displayed in exponential format with a base of 10, and the numerical values before and after the sign E indicate the mantissa and exponential part when the p-value is displayed in exponential format, respectively. ..

As a result, rs11065950, rs11066001, and rs144504271 were significantly associated with the genetic predisposition of facial redness, and were confirmed as SNPs that can determine facial redness. Furthermore, since the same results were obtained for SNPs that have a linkage disequilibrium relationship with each SNP, the tendency of the face to turn red for SNPs that have a linkage disequilibrium relationship with rs11065950, rs11066001, and rs144504271 was determined. It turned out that it could be judged. On the other hand, rs763035 and rs4417318, which have been suggested to be associated with alcohol and telangiectasia, were not significantly associated with the genetic predisposition to redness of the face.

According to the method of the present invention, it is possible to accurately and easily determine whether or not a subject has a genetic predisposition that tends to cause redness of the face. Therefore, based on the judgment result, it is possible to provide the subject with cosmetics and foods and drinks according to the tendency of the face to turn red, and to provide counseling and advice on the care method according to the tendency of the face to turn red. Will be.

Claims (7)

In the DNA-containing sample collected from the subject, the step of detecting one or more single nucleotide polymorphism (SNP) alleles of the following (a1) to (a6) and at least one of the detected allele bases. A method for determining the genetic predisposition to the tendency of the face to turn red, including the step of determining that the subject's face tends to turn red when one is a risk allele (however, the tendency of the face to turn red is the environment). And / or means the tendency of the face to turn red due to changes in mental status, excluding the tendency of the face to turn red due to drinking and skin diseases) .
(a1) SNP at the 101st base of the base sequence shown in SEQ ID NO: 1 (SNP: SNP specified by ID rs11065950 , risk allele is C )
(a2) The SNP in the 101st base of the base sequence shown in SEQ ID NO: 1 (SNP: SNP specified by ID rs11065950 , the risk allele is C ) and the SNP having a linkage disequilibrium coefficient r2 ≧ 0.8. , Rs numbers in the SNP database are rs3858705, rs11065939, rs7969300, rs58937998, rs11065953, rs10849958, rs7964109, rs6490187, rs10774626, rs11065946, rs118002600, rs7301158, rs11065941, rs11065959, rs11065960, rs11065963, rs11065965
(a3) SNP at the 101st base of the base sequence shown in SEQ ID NO: 5 (SNP: SNP specified by ID rs11066001 , risk allele is C )
(a4) The SNP in the 101st base of the base sequence shown in SEQ ID NO: 5 (SNP: SNP specified by ID rs11066001 , the risk allele is C ) and the SNP having a linkage disequilibrium coefficient r2 ≧ 0.8. , SNPs whose rs numbers in the SNP database are indicated by rs11066015, rs3782886
(a5) SNP at the 101st base of the base sequence shown in SEQ ID NO: 7 (SNP: SNP specified by ID rs144504271 , risk allele is A )
(a6) The SNP at the 101st base of the base sequence shown in SEQ ID NO: 7 (SNP: SNP specified by ID rs144504271 , the risk allele is A ) and the linkage disequilibrium coefficient r2 ≧ 0.8 . , SNP whose rs number in the SNP database is indicated by rs2074356 The SNP in the 101st base of the base sequence shown in SEQ ID NO: 1 in (a2) (SNP: SNP specified by ID rs11065950 , risk allele is C ) and SNP having a chain imbalance coefficient r2 ≧ 0.8 , SNP at the 101st base of the base sequence shown in SEQ ID NO: 2 (SNP: SNP specified by ID rs11065939 , risk allele is T ), SNP at the 101st base of the base sequence shown in SEQ ID NO: 3 (SNP) : SNP specified by ID rs7964109 , risk allele is G ), or SNP at the 101st base of the base sequence shown in SEQ ID NO: 4 (SNP: SNP specified by ID rs3815021 , risk allele is A ), The method according to claim 1. The SNP in the 101st base of the base sequence shown in SEQ ID NO: 5 in (a4) (SNP: SNP specified by ID rs11066001 , the risk allele is C ) and the SNP having a chain imbalance coefficient r2 ≧ 0.8 are , The method according to claim 1, wherein the SNP at the 101st base of the base sequence shown in SEQ ID NO: 6 (SNP: SNP specified by ID rs3782886 , the risk allele is C ). The SNP in the 101st base of the base sequence shown in SEQ ID NO: 7 of (a6) (SNP: SNP specified by ID rs144504271 , the risk allele is A ) and the SNP having a chain imbalance coefficient r2 ≧ 0.8 are , The method according to claim 1, wherein the SNP at the 101st base of the base sequence shown in SEQ ID NO: 8 (SNP: SNP specified by ID rs2074356 , the risk allele is A ). Based on the result determined by the method according to any one of claims 1 to 4, the subject is provided with cosmetics and / or foods and drinks according to the degree of genetic predisposition to the subject's facial redness. How to provide cosmetics and / or food and drink to be provided to. A cosmetology counseling method according to the degree of genetic predisposition to the tendency of a subject's face to turn red based on the result determined by the method according to any one of claims 1 to 4. SNP at the 101st base of the base sequence shown in SEQ ID NO: 1 (SNP: SNP specified by ID rs11065950), SNP at the 101st base of the base sequence shown in SEQ ID NO: 5 (SNP: ID rs11066001) SNP), SNP at the 101st base of the base sequence shown in SEQ ID NO: 7 (SNP: SNP specified by ID rs144504271) , SNP at the 101st base of the base sequence shown in SEQ ID NO: 2 (SNP: ID ) SNP specified by rs11065939), SNP at the 101st base of the base sequence shown in SEQ ID NO: 3 (SNP: SNP specified by ID rs7964109), SNP at the 101st base of the base sequence shown by SEQ ID NO: 4. (SNP: SNP specified by ID rs3815021), SNP at the 101st base of the base sequence shown in SEQ ID NO: 6 (SNP: SNP specified by ID rs3782886), or 101 of the base sequence shown in SEQ ID NO: 8. It is possible to amplify a sequence containing 10 or more bases containing an SNP (SNP: SNP specified by ID rs2074356) at the second base , a probe containing a complementary sequence thereof, and / or a region containing any of the above SNPs. A kit for determining the genetic predisposition to redness of a face, including a primer (however, the redness of the face means the redness of the face due to changes in the environment and / or mental state). , Excluding the tendency of the face to turn red due to drinking and skin diseases) .