JP2009022252A - Method for forecasting susceptibility toward exercise prescription aiming at improvement of lifestyle-related disease and augmentation of physical strength - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To identify the group of exercise prescription responsive genes, capable of being used for the genetic diagnosis of a susceptibility based on the expectation that the individual difference of the susceptibility toward the exercise prescription aiming at the improvement of life style-related diseases, prevention of cares, etc., is caused by a genetic diathesis, and a method for forecasting the susceptibility based on such the exercise prescription responsive genes. <P>SOLUTION: As the exercise prescription responsive gene group, e.g., those capable of being utilizable as the forecast of the improvement of systolic blood pressure (maximum blood pressure) by the exercise prescription are found out as follows. In β2 adrenalin receptors (hereinafter called as "ADRB2"), a mono base polymorphism such that whether the codon encoding an arginine residue at 175th position in the ADRB2 is CGG or AGG, is found. By identifying such the exercise prescription responsive genes, it becomes possible to forecast the improving effect of a subject by the exercise prescription, and based on the forecast, it is possible to propose a most suitable exercise prescription for the subject. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention is a method of predicting the improvement efficiency (sensitivity) of each individual based on exercise prescription (guidance of exercise amount, exercise intensity, exercise time, exercise frequency, etc.) based on the results of genetic diagnosis. The present invention relates to a method for predicting sensitivity to an exercise prescription for the purpose of prevention and / or enhancement of physical strength for prevention of care.

  Lifestyle-related diseases such as hypertension, hyperlipidemia, obesity, and diabetes are a general term for diseases that are considered to be caused mainly by lifestyle. In addition to environmental factors including lifestyle habits, genetic predisposition is involved in complex ways. These diseases are strongly involved in the development of ischemic heart disease, stroke, renal failure and the like. Therefore, it is considered that the onset of these serious diseases can be suppressed by improving or preventing these lifestyle-related diseases.

  Treatment of lifestyle-related diseases consists of non-drug therapy and drug therapy. Drug therapy is relatively expensive and, coupled with the anticipated increase in the number of patients, has had a major impact on national health care costs and how they are going.

  On the other hand, improvement of lifestyle habits, that is, improvement of dietary habits and exercise (exercise prescription) are effective in improving and preventing lifestyle-related diseases. In particular, exercise is less expensive than drug therapy, and exercise prescription is recommended before drug therapy, especially if symptoms are mild.

  However, there are individual differences in the sensitivity (degree, subject) for improving lifestyle-related diseases by exercise. In other words, there are those who can achieve a significant improvement in lifestyle-related diseases even though they are practicing the same exercise prescription, but the improvement is effective only for those who have little improvement or are not to be improved. Some are recognized. The former can be expected to improve lifestyle-related diseases effectively and economically without prescribing medication by applying exercise prescription. In the latter case, taking exercise prescriptions will lead to disadvantages such as unnecessarily burdening patients and giving them time to disease seriousness.

  If it is possible to predict susceptibility to improving lifestyle-related diseases by exercise on an individual basis, it is extremely useful in determining the treatment policy of non-drug therapy or drug therapy. In addition, based on the sensitivity prediction results, it is possible to perform exercise prescriptions effective for the person (instructing exercise amount, exercise intensity, exercise time, exercise frequency, etc.).

  Since some individual differences in susceptibility to and difficulty in lifestyle-related diseases are attributable to genetic predisposition, it is predicted that individual differences in susceptibility to lifestyle-related disease improvement due to exercise are also attributable to genetic predisposition . However, there is almost no scientific basis (report) on this point.

Patent Document 1 discloses a diagnostic method for predicting the risk of hypertension based on genetic information, and Patent Document 2 discloses a method for diagnosing the risk of cardiovascular disease based on genetic information. Is disclosed. Patent Document 3 discloses a method for predicting an individual's motor ability based on genetic information.
JP 2006-67902 A Special table 2001-509024 gazette JP 2005-538710 A

  The subject of the present invention is based on the prediction that individual differences in sensitivity to exercise prescriptions for the purpose of improving or preventing lifestyle-related diseases are also caused by genetic predisposition, and exercise prescription reactivity that can be used for genetic diagnosis of such sensitivity The purpose is to identify a gene group and propose a method for predicting sensitivity based on such an exercise prescription-responsive gene group.

  In addition, the problem of the present invention is based on the prediction that individual differences in sensitivity to exercise prescription for the purpose of enhancing physical fitness, which is recognized as effective in preventing lifestyle-related diseases and nursing care, are also caused by genetic predisposition. An object of the present invention is to identify a group of exercise prescription responsive genes that can be used for such genetic diagnosis of susceptibility, and to propose a method for predicting susceptibility based on such group of exercise prescription responsive genes.

  The present inventors have found that the following gene polymorphisms (a) to (e) can be used for predicting the improvement effect of systolic blood pressure (maximum blood pressure) by exercise prescription.

(A) In the β2 adrenergic receptor (hereinafter referred to as “ADRB2”) gene, a single nucleotide polymorphism defined by US National Center for Biotechnology Information (hereinafter referred to as NCBI) database registration number rs1042718, that is, the 175th arginine of ADRB2 Single nucleotide polymorphism of whether the codon encoding the residue is CGG or AGG
(A) In the arginine vasopressin 1A receptor (hereinafter referred to as “AVPR1A”) gene, a single nucleotide polymorphism defined by NCBI database registration number rs1042615, that is, a codon encoding the 136th phenylalanine residue of the AVPR1A is TTT. Single nucleotide polymorphism of whether it is TTC
(C) In a resistin (hereinafter referred to as “RETN”) gene, a single nucleotide polymorphism defined by the NCBI database registration number rs1862513, that is, a base in a nucleotide located 420 nucleotides upstream from the translation start point of the gene contains a cytosine residue. Single nucleotide polymorphism of group (C) or guanine residue (G)
(D) In the RETN gene, the single nucleotide polymorphism defined by NCBI database registration number rs3745367, that is, the base in the nucleotide located at position 181 of the second intron of the gene is an adenine residue (A) or a guanine residue Single nucleotide polymorphism of (G)
(E) In the methylenetetrahydrofolate reductase (hereinafter referred to as “MTHFR”) gene, a single nucleotide polymorphism defined by NCBI database registration number rs2274976, that is, a codon encoding the 594th amino acid of MTHFR encodes an arginine residue. Single nucleotide polymorphism of CGG that encodes or CAG that encodes a glutamine residue

  The present inventors have shown that the following polymorphisms of (f) and (g) are used to predict the effect of improving blood total cholesterol concentration by exercise prescription and / or the effect of improving blood LDL cholesterol concentration, respectively. It was found that it can be used for prediction.

(F) In the apolipoprotein C3 (hereinafter referred to as “APOC3”) gene, a single nucleotide polymorphism defined by NCBI database registration number rs5128, that is, a nucleotide in a nucleotide located 40 nucleotides downstream of the translation termination codon of the gene Single nucleotide polymorphism of cytosine residue (C) or guanine residue (G)
(G) Polynucleotide insertion / deletion polymorphism (I / D polymorphism) of 287 base pairs in the 16th intron of the angiotensin converting enzyme (hereinafter referred to as “ACE”) gene

  The present inventors have found that the above (ki) and the following polymorphisms (ku) to (ko) can be used for predicting the effect of reducing body fat percentage by exercise prescription.

(H) In the β3 adrenergic receptor (hereinafter referred to as “ADRB3”) gene, a single nucleotide polymorphism defined by NCBI database registration number rs4994, ie, the codon encoding the 64th amino acid of ADRB3 encodes an arginine residue. Single nucleotide polymorphism of CGG or TGG encoding tryptophan residue
(K) In the ADRB3 gene, a single nucleotide polymorphism defined by NCBI database registration number rs2071493, that is, the base in the nucleotide located at position 930 of the first intron of the gene is an adenine residue (A) or a guanine residue Single nucleotide polymorphism of (G)
(Co) In the α1A adrenergic receptor (hereinafter referred to as “ADRA1A”) gene, a single nucleotide polymorphism defined by NCBI database registration number rs1383914, that is, a nucleotide in a nucleotide located 563 nucleotides upstream from the translation start point of the gene -Nucleotide polymorphism of whether A is an adenine residue (A) or a guanine residue (G)

  The present inventors have found that the following polymorphisms (sa) and (si) can be used for predicting the improvement effect of the maximum oxygen intake by the exercise prescription, respectively.

(Sa) In the vascular endothelial lipase (hereinafter referred to as “LIPG”) gene, a single nucleotide polymorphism defined by NCBI database registration number rs2000813, that is, an ACA in which the codon encoding the 111th amino acid of LIPG encodes a threonine residue Or a single nucleotide polymorphism of ATA encoding an isoleucine residue
(Shi) In a stearate CoA desaturase (hereinafter referred to as “SCD”) gene, a single nucleotide polymorphism defined by NCBI database registration number rs3793768, that is, a base at a nucleotide located at position 1386 of the fourth intron of the gene, Single nucleotide polymorphism of guanine residue (G) or thymine residue (T)

  The present inventors have found that the following gene polymorphisms (S) can be used for predicting the improvement effect of exercise prescription on maximum oxygen intake, maximum heart rate, BMI, and blood glucose level.

(Su) In the ADRB2 gene, a single nucleotide polymorphism indicating whether the codon encoding the 16th amino acid of ADRB2 is AGA encoding an arginine residue or GGA encoding a glycine residue

  The present inventors have found that the following gene polymorphism of (C) can be used for predicting the improvement effect of BMI by exercise prescription.

(C) In the secreted frizzled-related protein 2 (hereinafter referred to as “SFRP2”) gene, the single nucleotide polymorphism defined by the NCBI database registration number rs3810765, that is, the base at the nucleotide located at the sixth intron of the SFRP2 gene is Single nucleotide polymorphism of cytosine residue (C) or thymine residue (T)

  The method for predicting susceptibility to an exercise prescription according to the present invention is based on such findings, and is a type of exercise prescription responsive gene that causes individual differences in sensitivity to an exercise prescription for the purpose of improving lifestyle diseases and / or enhancing physical fitness. Is examined with a sample collected from the subject, and based on the type of the exercise prescription responsive gene, the subject's sensitivity to the exercise prescription for the purpose of improving lifestyle diseases and / or enhancing physical fitness is predicted.

    The exercise prescription responsive gene includes at least one of the following genes (1) to (11).

(1) β2 adrenergic receptor (hereinafter referred to as “ADRB2”) gene
(2) Arginine vasopressin 1A receptor (hereinafter referred to as “AVPR1A”) gene
(3) Resistin (hereinafter referred to as “RETN”) gene
(4) Methylenetetrahydrofolate reductase (hereinafter referred to as “MTHFR”) gene
(5) Apolipoprotein C3 (hereinafter referred to as “APOC3”) gene
(6) Angiotensin converting enzyme (hereinafter referred to as “ACE”) gene
(7) β3 adrenergic receptor (hereinafter referred to as “ADRB3”) gene
(8) α1A adrenergic receptor (hereinafter referred to as “ADRA1A”) gene
(9) Vascular endothelial lipase (hereinafter referred to as “LIPG”) gene
(10) Stearate CoA desaturase (hereinafter referred to as “SCD”) gene
(11) Secreted frizzled-related protein 2 (hereinafter referred to as “SFRP2”) gene

  The present inventors have identified the above-mentioned exercise prescription responsive gene from a sample such as blood collected from a subject, and confirmed that a difference in response (sensitivity) to each individual's exercise prescription can be predicted based on the identification result.

  In the prediction method of the present invention, an exercise prescription responsive gene is found in advance, and the sensitivity to an exercise prescription for the purpose of improving lifestyle diseases and enhancing physical fitness is examined for each type of exercise prescription responsive gene. Then, a sample such as blood of the subject is collected, nucleic acid molecules are extracted therefrom, and the type of the exercise prescription responsive gene is identified by a well-known identification direction. Based on this result, the sensitivity (improvement efficiency) regarding exercise prescription, for example, lifestyle-related disease improvement and physical strength enhancement by interval walking is predicted. Then, for example, for a subject who is predicted not to be sufficiently expected to improve lifestyle-related diseases, a prescription such as adopting drug therapy is determined. It should be noted that the method of the present invention can be similarly applied to all animals (mouse, rat, rabbit, cat, dog, monkey, etc.) carrying the exercise prescription responsive gene.

  First, gene analysis performed to find an exercise prescription responsive gene will be described. In the following genetic analysis, 201 women (average age 64.8 ± 6.1 years) and 99 men (average age) who practiced exercise prescription with interval walking at Matsumoto Junior College of Physical Education for 6 months 70.1 ± 6.0 years).

  Interval fast walking is an exercise method in which normal walking (or slow walking) and rapid walking are repeated at regular intervals, for example, every 3 minutes. Typical examples of specific exercise methods are as follows. Usually walk at the end / end of walking. Normal walking is a guide for walking speed and time to correct the disorder of breathing during fast walking. To walk fast, swing your arms, take a large stride, and walk fast. At this time, it walks at a speed exceeding a preset target exercise intensity according to the physical strength of the individual. Walk fast so that you can keep the same speed from start to finish.

  Measure blood pressure, total blood cholesterol level, LDL cholesterol level, body fat percentage, maximum oxygen intake, and initial values for BMI, and values after continuous exercise for 6 months. Calculated.

  The analysis of the effect of improving systolic blood pressure was conducted on 59 women and 42 men whose initial value of systolic blood pressure was 140 mmHg or higher, which is a reference value clinically defined as hypertension.

  The analysis of the effect of improving the total cholesterol concentration was conducted on 96 women and 31 men whose initial value of blood total cholesterol concentration was 220 mg / dl or more, which is a reference value clinically defined as hyperlipidemia. It was.

  The analysis of the improvement effect of LDL cholesterol concentration was conducted on 79 women and 31 men whose initial value of blood LDL cholesterol concentration was 140 mg / dl or higher, which is a reference value clinically defined as hyperlipidemia. It was.

  The analysis of the effect of improving body fat percentage was performed on 143 women whose initial body fat percentage was 30% or more.

  The analysis of the effect of improving the maximum oxygen intake was conducted on all subjects.

  The analysis of the improvement effect of BMI was conducted on 40 women and 24 men whose initial values of BMI were 25 or more, which is a reference value clinically defined as obesity.

  Prior to gene analysis, informed consent about gene analysis was obtained from all subjects and anonymization was possible.

(Example 1: Association between rs1042718 polymorphism in ADRB2 gene and diastolic blood pressure improvement effect by exercise)
For the rs1042718 polymorphism in the ADRB2 gene, subjects were typed by TaqMan PCR.

  Next, the obtained data was analyzed by t-test, and the amount of decrease in systolic blood pressure due to exercise was compared between each genotype holder. The results are shown in Table 1 below.

[Table 1]
Between AA and C allele carriers in the ADRB2 intragenic rs1042718 polymorphism,
Comparison of decrease in systolic blood pressure due to exercise (t test)

  In the comparison of the maximum blood pressure reduction amount, it was 5.2 ± 12.4 mmHg in the AA type holder, whereas it was 13.0 ± 12.0 mmHg in the C allele holder, and a significant difference was observed (P = 0.0053).

(Example 2: Association of rs1042615 polymorphism in AVPR1A gene with the effect of improving systolic blood pressure by exercise)
For the rs1042615 polymorphism in the AVPR1A gene, the subject was typed by TaqMan PCR.

  Next, the obtained data was analyzed by t-test, and the amount of decrease in systolic blood pressure due to exercise was compared between each genotype holder. The results are shown in Table 2 below.

[Table 2]
Between CC type holder and T allele holder in the rs1042615 polymorphism in AVPR1A gene,
Comparison of decrease in systolic blood pressure due to exercise (t test)

  In comparison of the maximum blood pressure reduction amount, it was 4.0 ± 14.1 mmHg in the CC type holder, whereas it was 12.8 ± 11.7 mmHg in the T allele holder, showing a significant difference (P = 0.0029).

Example 3: Relationship between rs1862513 polymorphism in RETN gene and effect of improving systolic blood pressure by exercise)
For the rs1862513 polymorphism in the RETN gene, the subject was typed by TaqMan PCR.

  Next, the obtained data was analyzed by t-test, and the amount of decrease in systolic blood pressure due to exercise was compared between each genotype holder. The results are shown in Table 3 below.

[Table 3]
Between CC type holders and G allele holders in the rs1862513 polymorphism in the RETN gene,
Comparison of decrease in systolic blood pressure due to exercise (t test)

  In comparison of the amount of decrease in maximum blood pressure, it was 1.8 ± 10.3 mmHg for the CC-type holder, and 11.7 ± 12.8 mmHg for the G allele holder, indicating a significant difference (P = 0.0199).

(Example 4: Association between rs3745367 polymorphism in RETN gene and maximal blood pressure improvement effect by exercise)
For the rs3745367 polymorphism in the RETN gene, subjects were typed by TaqMan PCR.

  Next, the obtained data was analyzed by t-test, and the amount of decrease in systolic blood pressure due to exercise was compared between each genotype holder. The results are shown in Table 4 below.

[Table 4]
Between AA type carriers and G allele carriers in the rs3745367 polymorphism in the RETN gene,
Comparison of decrease in systolic blood pressure due to exercise (t test)

  In comparison of the maximum blood pressure reduction amount, it was 2.5 ± 11.1 mmHg in the AA type holder, and 11.9 ± 12.7 mmHg in the G allele holder, showing a significant difference (P = 0.0123).

(Example 5: Relationship between rs2274976 polymorphism in MTHFR gene and the effect of improving systolic blood pressure by exercise)
For the rs2274976 polymorphism in the MTHFR gene, the subject was typed by TaqMan PCR.

  Next, the obtained data was analyzed by t-test, and the amount of decrease in systolic blood pressure due to exercise was compared between each genotype holder. The results are shown in Table 5 below.

[Table 5]
Between GG type holder and A allele holder in rs2274976 polymorphism in MTHFR gene,
Comparison of decrease in systolic blood pressure due to exercise (t test)

  In comparison of the maximum blood pressure reduction amount, it was 11.7 ± 13.1 mmHg in GG type holders and 4.3 ± 9.3 mmHg in A allele holders, showing a significant difference (P = 0.0429).

(Example 6: Association of rs5128 polymorphism in APOC3 gene with blood total cholesterol concentration by exercise and LDL cholesterol concentration improving effect)
For the rs5128 polymorphism in the APOC3 gene, subjects were typed by TaqMan PCR.

  Next, the obtained data was analyzed by t-test, and the amount of change in blood total cholesterol concentration due to exercise was compared between each genotype holder. The results are shown in Table 6A below.

[Table 6A]
Between CC type holder and G allele holder in rs5128 polymorphism in APOC3 gene,
Comparison of changes in blood total cholesterol concentration due to exercise (t-test)

  In comparison of changes in total blood cholesterol concentration, it was + 4.7 ± 15.7 mg / dl for CC type carriers, while -10.5 ± 17.7 mg / dl for G alleles, a significant difference was observed. (P = 0.0012).

  Next, the obtained data was analyzed by t-test, and the amount of change in blood LDL cholesterol concentration due to exercise was compared between each genotype holder. The results are shown in Table 6B below.

[Table 6B]
Between CC type holder and G allele holder in rs5128 polymorphism in APOC3 gene,
Comparison of changes in blood LDL cholesterol concentration due to exercise (t-test)

  In comparison of changes in blood LDL cholesterol concentration, it was + 1.6 ± 16.0 mg / dl for CC type carriers, while -10.1 ± 18.8 mg / dl for G alleles, a significant difference was observed. (P = 0.003).

(Example 7: Relationship between I / D polymorphism in ACE gene and blood LDL cholesterol level improvement effect by exercise)
Regarding the I / D polymorphism in the ACE gene, the subject was typed by PCR / agarose gel electrophoresis.

  Next, the obtained data was analyzed by t-test, and the amount of change in blood LDL cholesterol concentration due to exercise was compared between each genotype holder. The results are shown in Table 7 below.

[Table 7]
Between DD type holder and I allele holder in ACE intragenic I / D polymorphism,
Comparison of changes in blood LDL cholesterol concentration due to exercise (t-test)

  In comparison of changes in blood LDL cholesterol concentration, DD type holders showed -23.0 ± 22.1mg / dl, while I allele holders showed -7.0 ± 17.4mg / dl, showing a significant difference. (P = 0.0059).

(Example 8: Relationship between rs4994 polymorphism in ADRB3 gene and body fat percentage improvement effect by exercise)
For the rs4994 polymorphism in the ADRB3 gene, subjects were typed by TaqMan PCR.

  Next, the obtained data was analyzed by t-test, and the decrease in body fat percentage due to exercise was compared between each genotype holder. The results are shown in Table 8 below.

[Table 8]
Between TT type holder and C allele holder in rs4994 polymorphism in ADRB3 gene,
Comparison of decrease in body fat percentage due to exercise (t test)

  In comparison of the decrease in body fat percentage, it was 1.35 ± 1.13% for TT type holders and 2.32 ± 1.33% for C allele holders, showing a significant difference (P <0.0001).

(Example 9: Association between rs2071493 polymorphism in ADRB3 gene and body fat percentage improvement effect by exercise)
Regarding the rs2071493 polymorphism in the ADRB3 gene, the subject was typed by TaqMan PCR.

  Next, the obtained data was analyzed by t-test, and the decrease in body fat percentage due to exercise was compared between each genotype holder. The results are shown in Table 9 below.

[Table 9]
Between GG type holder and A allele holder in rs2071493 polymorphism in ADRB3 gene,
Comparison of decrease in body fat percentage due to exercise (t test)

  In comparison of the decrease in body fat percentage, it was 1.34 ± 1.13% for GG type holders and 2.32 ± 1.33% for A allele holders, showing a significant difference (P <0.0001).

(Example 10: Association between rs1383914 polymorphism in ADRA1A gene and body fat percentage improvement effect by exercise)
For the rs1383914 polymorphism in the ADRA1A gene, the subject was typed by TaqMan PCR.

  Next, the obtained data was analyzed by t-test, and the decrease in body fat percentage due to exercise was compared between each genotype holder. The results are shown in Table 10 below.

[Table 10]
Between AA and G allele carriers in the ADRA1A intragenic rs1383914 polymorphism,
Comparison of decrease in body fat percentage due to exercise (t test)

  In the comparison of the decrease in body fat percentage, it was 2.22 ± 1.21% for AA type holders and 1.51 ± 1.27% for G allele holders, showing a significant difference (P = 0.0063).

(Example 11: Relationship between I / D polymorphism in ACE gene and body fat percentage improvement effect by exercise)
Regarding the I / D polymorphism in the ACE gene, the subject was typed by PCR / agarose gel electrophoresis.

  Next, the obtained data was analyzed by t-test, and the decrease in body fat percentage due to exercise was compared between each genotype holder. The results are shown in Table 11 below.

[Table 11]
Between DD type holder and I allele holder in ACE intragenic I / D polymorphism,
Comparison of decrease in body fat percentage due to exercise (t test)

  In comparison of the decrease in body fat percentage, it was 2.79 ± 1.01% for DD type holders and 1.54 ± 1.24% for I allele holders, showing a significant difference (P = 0.0004).

(Example 12: Relationship between rs2000813 polymorphism in LIPG gene and maximum oxygen uptake improvement effect by exercise)
For the rs2000813 polymorphism in the LIPG gene, the subjects were typed by TaqMan PCR.

  Next, the obtained data was analyzed by t-test, and the increase in the maximum oxygen intake due to exercise was compared between each genotype holder. The results are shown in Table 12 below.

[Table 12]
Between CC type holder and T allele holder in rs2000813 polymorphism in LIPG gene,
Comparison of increase in maximum oxygen intake by exercise (t test)

  In comparison of the maximum increase in oxygen uptake, it was 3.5 ± 3.2 ml / kg / min for CC type holders, while 1.1 ± 3.4 ml / kg / min for T allele holders, showing a significant difference. (P = 0.003).

(Example 13: Relationship between the rs3793768 polymorphism in the SCD gene and the effect of improving maximum oxygen intake by exercise)
For the rs3793768 polymorphism in the SCD gene, the subject was typed by TaqMan PCR.

  Next, the obtained data was analyzed by t-test, and the increase in the maximum oxygen intake due to exercise was compared between each genotype holder. The results are shown in Table 13 below.

[Table 13]
Between GG type holder and C allele holder in rs3793768 polymorphism in SCD gene,
Comparison of increase in maximum oxygen intake by exercise (t test)

  In comparison of increase in maximum oxygen intake, GG holders have 0.2 ± 2.2 ml / kg / min, whereas C allele holders have 1.5 ± 3.6 ml / kg / min, showing a significant difference. (P = 0.03).

(Example 14: Association between rs3810765 polymorphism in SFRP2 gene and BMI improvement effect by exercise)
For the rs3810765 polymorphism in the SFRP2 gene, the subject was typed by TaqMan PCR.

  Next, the obtained data was analyzed by t-test, and the amount of decrease in BMI due to exercise was compared between each genotype holder. The results are shown in Table 14 below.

[Table 14]
Between TT type holder and C allele holder in rs3810765 polymorphism in SFRP2 gene,
Comparison of BMI reduction due to exercise (t test)

  In the comparison of BMI reduction amount, it was 0.26 ± 0.58 for TT type holders, while 0.70 ± 0.62 for C allele holders, showing a significant difference (P = 0.01).

(Example 15: Association between polymorphism in ADRB2 gene and physical fitness enhancement effect)
In Example 15, as in Examples 1 to 14, the subject was a person who performed an exercise prescription by rapid walking at an interval in Matsumoto City Junior College, but the implementation period was 17 months.

  When the person who has Arg16 / Arg type (n = 44) and the person who has Gly16 / Gly type (n = 87) in the 16th amino acid polymorphism of ADRB2 is compared, walking rate during training period Were 0.50 ± 0.03 for Arg16 / Arg type and 0.52 ± 0.02 for Gly16 / Gly type, and there was no significant difference between groups. The walking time during the period was 24 ± 1 for Arg16 / Arg type carriers and 24 ± 1 min / day for Gly16 / Gly type carriers, and there was no significant difference between the groups. The rapid walking energy consumption was 103 ± 8 for Arg16 / Arg type holders and 104 ± 6 kcal / day for Gly16 / Gly type holders, and there was no significant difference between groups.

  The maximum oxygen intake before training was 21.7 ± 0.6 for Arg16 / Arg type holders and 20.6 ± 0.4 ml / min / kg for Gly16 / Gly type holders. After interval training for 17 months, it increased to 27.1 ± 0.9 for Arg16 / Arg type holders and 25.3 ± 0.5 ml / min / kg for Gly16 / Gly type holders, compared with Gly16 / Gly type holders. It was high in the Arg16 / Arg type holder (P <0.05).

  The maximum heart rate when measuring endurance before training was 127 ± 2 for Arg16 / Arg type holders and 124 ± 2 beats / min for Gly16 / Gly type holders. After 17 months of interval training, Arg16 / Arg type holders increased to 143 ± 2 and Gly16 / Gly type holders increased to 136 ± 2 beats / min, which was higher than that of Gly16 / Gly holders. High in type holders (P <0.05).

BMI before training, 23.6 ± 0.5 at Argl6 / Arg type holders, no significant differences were observed between 24.1 ± 0.4kg / m ² and the group at Gly16 / Gly-type holders. After interval training for 17 months, Arg16 / Arg type holders decreased to 22.4 ± 0.4, and Gly16 / Gly type holders dropped to 23.2 ± 0.3 kg / m ² , compared with Gly16 / Gly type holders. Arg16 / Arg type holders showed a low tendency.

  Blood glucose levels before training were 104 ± 2 for Arg16 / Arg type holders and 110 ± 2 mg / dl for Gly16 / Gly type holders, significantly lower in Arg16 / Arg type holders (P <0.05). . After 17 months of interval training, Arg16 / Arg type holders decreased to 97 ± 2 and Gly16 / Gly type holders decreased to 104 ± 2 mg / dl, compared with Gly16 / Gly type holders. It was low in Arg type holders (P <0.05).

  As described above, several exercise prescription responsive genes were found, and each type of exercise prescription responsive gene revealed susceptibility to exercise prescriptions aimed at improving lifestyle-related diseases and / or enhancing physical fitness became.

  Next, a sample such as blood of the subject is collected, nucleic acid molecules are extracted therefrom, and the type of exercise prescription responsive gene is identified by a well-known identification direction. And based on this result, for example, the sensitivity (improvement efficiency) regarding lifestyle-related disease improvement and physical strength enhancement due to interval walking is predicted. Then, for example, for a subject who is predicted not to be sufficiently expected to improve lifestyle-related diseases, a prescription such as adopting drug therapy is determined.

Claims (20)

Check the type of a specific gene or gene group (hereinafter referred to as an exercise prescription responsive gene or an exercise prescription responsive gene group) for sensitivity to exercise prescriptions aimed at improving lifestyle-related diseases and / or enhancing physical fitness,
Sensitivity to exercise prescription characterized by predicting sensitivity to exercise prescription for the purpose of improving lifestyle-related diseases and / or enhancing physical fitness based on the type of exercise prescription responsive gene or exercise prescription responsive gene group How to predict. In claim 1,
The exercise prescription responsive gene has a plurality of genotypes (hereinafter referred to as polymorphisms), and the sensitivity to the exercise prescription is significantly different among at least two genotypes as a result of statistical analysis. How to predict sensitivity to exercise prescription. In claim 1 or 2,
The method for predicting sensitivity to an exercise prescription, wherein the exercise prescription responsive gene is at least one of the following (1) to (11).
(1) β2 adrenergic receptor (hereinafter referred to as “ADRB2”) gene (2) arginine vasopressin 1A receptor (hereinafter referred to as “AVPR1A”) gene (3) resistin (hereinafter referred to as “RETN”) gene (4) methylenetetrahydrofolic acid Reductase (hereinafter referred to as “MTHFR”) gene (5) Apolipoprotein C3 (hereinafter referred to as “APOC3”) gene (6) Angiotensin converting enzyme (hereinafter referred to as “ACE”) gene (7) β3 adrenergic receptor (hereinafter referred to as “ADRB3”) (8) α1A adrenergic receptor (hereinafter referred to as “ADRA1A”) gene (9) Vascular endothelial lipase (hereinafter referred to as “LIPG”) gene (10) Stearate CoA desaturase (hereinafter referred to as “SCD”) gene ( 11) Secreted frizzled-related protein 2 (hereinafter referred to as “SFRP2”) Gene In any one of claims 1 to 3,
The method for predicting sensitivity to an exercise prescription, wherein the sensitivity is any one or more of the following.
a) Effect of improving blood pressure b) Effect of improving blood total cholesterol concentration c) Effect of improving blood LDL cholesterol concentration d) Effect of improving body fat percentage e) Effect of improving Body Mass Index (hereinafter referred to as BMI) f) Blood glucose G) Improvement effect of maximum oxygen uptake h) Improvement effect of maximum heart rate In any one of claims 1 to 4,
The method of predicting sensitivity to an exercise prescription, wherein the exercise prescription includes at least one instruction of exercise amount, exercise intensity, exercise time, and exercise frequency. In claim 1,
Identifying whether the codon encoding the 175th arginine residue in the nucleotide sequence of the ADRB2 gene of the specimen is a single nucleotide polymorphism of CGG or AGG,
A method for predicting sensitivity to an exercise prescription characterized by predicting an improvement effect on systolic blood pressure (maximum blood pressure) based on the identification result. In claim 1,
In the sample ADRB2 gene, identify whether the codon encoding the 16th amino acid of ADRB2 is AGA encoding arginine residue or GGA encoding glycine residue,
A method for predicting sensitivity to an exercise prescription characterized by predicting at least one improvement effect of maximum oxygen intake, maximum heart rate, BMI, and blood glucose level based on the identification result. In claim 1,
In the sample AVPR1A gene, identify whether the codon encoding the 136th phenylalanine residue of AVPR1A is a single nucleotide polymorphism of TTT or TTC,
A method for predicting sensitivity to an exercise prescription characterized by predicting an improvement effect on systolic blood pressure (maximum blood pressure) based on the identification result. In claim 1,
Identifying whether the nucleotide in the nucleotide located 420 nucleotides upstream of the translation start point in the sample RETN gene is a single nucleotide polymorphism of cytosine residue (C) or guanine residue (G),
A method for predicting sensitivity to an exercise prescription characterized by predicting an improvement effect on systolic blood pressure (maximum blood pressure) based on the identification result. In claim 1,
Identifying whether the nucleotide base located at position 181 of the second intron in the RENT gene of the specimen is a single nucleotide polymorphism of an adenine residue (A) or a guanine residue (G),
A method for predicting sensitivity to an exercise prescription characterized by predicting an improvement effect on systolic blood pressure (maximum blood pressure) based on the identification result. In claim 1,
In the MTHFR gene of the specimen, identify whether the codon encoding the 594th amino acid of MTHFR is a single nucleotide polymorphism of CGG encoding an arginine residue or CAG encoding a glutamine residue,
A method for predicting sensitivity to an exercise prescription characterized by predicting an improvement effect on systolic blood pressure (maximum blood pressure) based on the identification result. In claim 1,
Identifying whether the nucleotide in the nucleotide located 40 nucleotides downstream of the translational stop codon of the APOC3 gene of the specimen is a single nucleotide polymorphism of a cytosine residue (C) or a guanine residue (G),
A method for predicting sensitivity to an exercise prescription characterized by predicting at least one improvement effect of blood total cholesterol concentration and blood LDL cholesterol concentration based on the identification result. In claim 1,
Identifying an insertion / deletion polymorphism of a 287 base pair polynucleotide chain within the 16th intron of the specimen ACE gene;
A method for predicting sensitivity to an exercise prescription characterized by predicting an effect of improving blood LDL cholesterol concentration based on an identification result. In claim 1,
In the sample ADRB3 gene, the codon encoding the 64th amino acid of ADRB3 is identified as a single nucleotide polymorphism of CGG encoding arginine residue or TGG encoding tryptophan residue,
A method for predicting sensitivity to an exercise prescription characterized by predicting an effect of decreasing body fat percentage based on an identification result. In claim 1,
Identifying which single nucleotide polymorphism of the adenine residue (A) or the guanine residue (G) is in the nucleotide at position 930 of the first intron of the ADRB3 gene of the specimen,
A method for predicting sensitivity to an exercise prescription characterized by predicting an effect of decreasing body fat percentage based on an identification result. In claim 1,
Identifying whether the base in the nucleotide located 563 nucleotides upstream from the translation start point of the ADRA1A gene of the specimen is a single nucleotide polymorphism of an adenine residue (A) or a guanine residue (G),
A method for predicting sensitivity to an exercise prescription characterized by predicting an effect of decreasing body fat percentage based on an identification result. In claim 1,
Identifying an insertion / deletion polymorphism of a 287 base pair polynucleotide chain within the 16th intron of the specimen ACE gene;
A method for predicting sensitivity to an exercise prescription characterized by predicting an effect of decreasing body fat percentage based on an identification result. In claim 1,
In the sample LIPG gene, the codon encoding the 111th amino acid of LIPG is identified as an ACA encoding a threonine residue or an ATA encoding an isoleucine residue,
A method for predicting sensitivity to an exercise prescription characterized by predicting the improvement effect of maximum oxygen intake, which is an index of endurance physical strength, based on the identification result. In claim 1,
Identify whether the nucleotide in the 1386th nucleotide of the fourth intron of the SCD gene of the specimen is a single nucleotide polymorphism of guanine residue (G) or thymine residue (T),
A method for predicting sensitivity to an exercise prescription characterized by predicting the improvement effect of maximum oxygen intake, which is an index of endurance physical strength, based on the identification result. In claim 1,
Identify whether the nucleotide in the 6th nucleotide of the first intron of the sample SFRP2 gene is a single nucleotide polymorphism of cytosine residue (C) or thymine residue (T),
A method for predicting sensitivity to an exercise prescription characterized by predicting the improvement effect of BMI based on the identification result.