Method for determining the presence or absence of a genetic predisposition for high serum uric acid levels after menopause, method for detecting single nucleotide polymorphism (SNP) alleles, composition, and kit

Abstract

To provide a method for determining the hyperuricemia affection risk of an adult female.SOLUTION: A method for determining the presence of a genetic factor showing high serum uric acid levels after menopause, where the method includes a determination process in which it is determined that a subject being an adult female has a genetic factor that serum uric acid levels of the subject show high values after menopause when at least one of the following single nucleotide polymorphism (SNP) (a) to (c) of a nucleic acid derived from the subject is a risk allele, and it is determined that the subject does not have the genetic factor that the serum uric acid levels of the subject show high values after menopause when any of the above single nucleotide polymorphism (SNP) is not a risk allele. The risk allele, when average serum uric acid levels in populations each having 2 kinds of homozygous type are obtained and compared, constitutes a homozygous type which shows a higher value of an average serum uric acid level than the other homozygous type, and the high serum uric acid levels and high values about serum uric acid levels mean that the serum uric acid levels are 7 mg / dL or more. (a) rs1351879 on human chromosome 2, (b) rs4430896 on human chromosome 2, and (c) rs117377116 on human chromosome 12.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for determining the presence or absence of a genetic predisposition to high serum uric acid levels after menopause, and a method, composition, and kit for detecting alleles of single nucleotide polymorphisms (SNPs) (a) to (c). [Background technology]

[0002] A condition in which serum uric acid levels exceed the normal range (7 mg / dL or higher; high serum uric acid levels) is called hyperuricemia. Some patients with hyperuricemia develop a bout of arthritis known as "gout," significantly reducing their quality of life (QOL). In recent years, it has also been noted that hyperuricemia can cause vascular disorders of the heart and brain, as well as impaired kidney function. When examining the relationship between the incidence of end-stage renal failure and hyperuricemia, the incidence rate per 1,000 people is 1.22 for those with uric acid levels below 7 mg / dL, and 4.64 for those with hyperuricemia. Therefore, it has become necessary to consider the risk of developing hyperuricemia, not just from the perspective of gout.

[0003] It has been known that both genetic predisposition and environmental factors are involved in the onset of hyperuricemia and serum uric acid levels. Obesity is known to be a major environmental factor in the onset of hyperuricemia, and lifestyle modification is considered effective for prevention. On the other hand, elucidating genetic predisposition is important from the perspective of enabling effective prevention of hyperuricemia taking into account individual characteristics, and several uric acid-related genes have been reported as genetic predisposition factors for this disease (e.g., Non-Patent Document 1). [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Nakatochi, M. et al. Genome-wide meta-analysis identifies multiple novel loci associated with serum uric acid levels in Japanese individuals. Commun Biol 2, 115 (2019).(https: / / doi.org / 10.1038 / s42003-019-0339-0) Summary of the Invention [Problem to be solved by the invention]

[0005] The prevalence of hyperuricemia is significantly higher in men than in women. Therefore, most of the findings related to genetic predispositions related to serum uric acid levels have been based on data from a high male population. Therefore, there has been a lack of knowledge about genetic predispositions related to serum uric acid levels in women.

[0006] Therefore, an object of the present invention is to provide a method for determining the risk of hyperuricemia in adult women. [Means for solving the problem]

[0007] The present inventors have focused on the fact that serum uric acid levels tend to increase in adult women after menopause when the female hormone estrogen decreases, and have discovered genetic factors that contribute to high serum uric acid levels after menopause, leading to the completion of the present invention. More specifically, the present invention provides the following.

[0008] [1] A method for determining whether or not there is a genetic predisposition to high serum uric acid levels after menopause, the method comprising: The method includes a step of determining that the subject has a genetic predisposition to postmenopausal high serum uric acid levels when at least one of the following single nucleotide polymorphisms (SNPs) (a) to (c) in a nucleic acid derived from an adult female subject is a risk allele, and determining that the subject does not have a genetic predisposition to postmenopausal high serum uric acid levels when none of the above single nucleotide polymorphisms (SNPs) is a risk allele, The risk allele is an allele that constitutes a homozygous type whose average serum uric acid value is higher than that of the other homozygous type when the average serum uric acid value is calculated and compared in a population having each of two types of homozygous types, The method, wherein the high serum uric acid level and the high value for serum uric acid level are serum uric acid levels of 7 mg / dL or higher. (a) rs1351879 on human chromosome 2 (b) rs4430896 on human chromosome 2 (c) rs117377116 on human chromosome 12

[0009] [2] The risk allele of the above single nucleotide polymorphism (SNP) (a) is A, The risk allele of the single nucleotide polymorphism (SNP) (b) is G, The method according to [1] above, wherein the risk allele of the single nucleotide polymorphism (SNP) (c) is A.

[0010] [3] The method according to [1] or [2] above, wherein the subject is a premenopausal adult female who has not yet shown high serum uric acid levels after menopause at the time of assessment. [4] The method according to any one of [1] to [3] above, which is for determining whether or not there is a risk of showing high serum uric acid levels after menopause before or at an early stage of the onset of hyperuricemia and / or a disease or condition associated with hyperuricemia.

[0011] [5] The method described in [4] above, wherein the disease or condition associated with hyperuricemia is at least one selected from the group consisting of gout, gouty arthritis, cardiac or cerebrovascular disorders, myocardial infarction, kidney stones, urinary tract stones (including ureteral stones and bladder stones), decreased kidney function, chronic kidney disease, and renal failure. [6] The method according to any one of [1] to [5] above, which is used to detect the risk of the subject in developing hyperuricemia and / or a disease or condition associated with hyperuricemia, to take preventive measures to reduce the risk (including improving lifestyle habits and monitoring serum uric acid levels), to detect hyperuricemia and / or a disease or condition associated with hyperuricemia in the subject, and / or to select a subject having hyperuricemia and / or a disease or condition associated with hyperuricemia.

[0012] [7] The method according to any one of [1] to [6] above, comprising a detection step of detecting at least one allele of the single nucleotide polymorphisms (SNPs) (a) to (c). [8] A method for detecting at least one allele of the single nucleotide polymorphisms (SNPs) (a) to (c) for use in the method according to any one of [1] to [7] above.

[0013] [9] At least one allele of the above single nucleotide polymorphisms (SNPs) (a) to (c) can be detected by scanning probe and nanopore DNA sequencing, pyrosequencing, denaturing gradient gel electrophoresis (DGGE), time-temperature gradient electrophoresis (TTGE), Zn(II)-cyclen polyacrylamide gel electrophoresis, homogeneous fluorescent PCR-based single nucleotide polymorphism analysis, phosphate-affinity polyacrylamide gel electrophoresis, high-throughput SNP genotyping platforms, molecular beacons, 5' nuclease reactions, Taqman assays, MassArray (single-base primer extension coupled with matrix-assisted laser desorption / ionization time-of-flight mass spectrometry), trityl mass tags, and genotyping platforms (Invader Assay (registered trademark), single base primer extension (SBE) assay, PCR amplification (e.g., PCR amplification on magnetic nanoparticles (MNPs)), restriction enzyme analysis of PCR products (RFLP method), allele-specific PCR, multiple primer extension (MPEX), isothermal smart amplification, PCR-SSCP (single-stranded conformation polymorphism analysis), sequencing, ARMS (Amplification Refracting Mutation System), and RNAse A cleavage method.

[0014]

[10] A composition for use in the method according to any one of [1] to [9] above, the composition comprising a reagent capable of directly or indirectly detecting at least one allele of the single nucleotide polymorphisms (SNPs) (a) to (c).

[11] A kit for use in the method according to any one of [1] to [9] above, the kit comprising a reagent capable of directly or indirectly detecting at least one allele of the single nucleotide polymorphisms (SNPs) (a) to (c).

[12] The composition according to

[10] or the kit according to

[11] , wherein the reagent is selected from an oligonucleotide, a DNA probe, an RNA probe, and a ribozyme. [Effects of the Invention]

[0015] According to the present invention, a method for determining the risk of hyperuricemia in adult women can be provided. [Brief explanation of the drawings]

[0016] [Figure 1] FIG. 1 shows the analysis results of SNPs (a) to (c) in Example 1. DETAILED DESCRIPTION OF THE INVENTION

[0017] Hereinafter, an embodiment of the present invention will be described, but the present invention is not limited to this.

[0018] <Method for determining whether or not there is a genetic predisposition to high serum uric acid levels after menopause> A first aspect of the present invention is a method for determining the presence or absence of a genetic predisposition to high serum uric acid levels after menopause, the method comprising: The method includes a determination step of determining that the subject has a genetic predisposition to high serum uric acid levels after menopause when at least one of the single nucleotide polymorphisms (SNPs) (a) to (c) described below in nucleic acid derived from the adult female subject is a risk allele, and determining that the subject does not have a genetic predisposition to high serum uric acid levels after menopause when none of the single nucleotide polymorphisms (SNPs) are risk alleles.

[0019] The method of the first aspect of the present invention focuses on the fact that serum uric acid levels tend to increase in adult women after menopause when the female hormone estrogen decreases, and can be said to be a method for determining a genetic predisposition for postmenopausal elevated serum uric acid levels. Based on the presence or absence of such genetic predisposition or genetic factor, the risk of postmenopausal elevated serum uric acid levels in an adult female subject can be determined. Specifically, when at least one SNP site (site where SNPs are detected) among the single nucleotide polymorphisms (SNPs) (a) to (c) described below is detected in genome-derived nucleic acid (DNA) extracted from a biological sample of an adult female subject, the method determines whether the subject is prone to postmenopausal elevated serum uric acid levels based on the SNP allele information.

[0020] As used herein, "high serum uric acid level" refers to a serum uric acid level exceeding the reference value for diagnosing hyperuricemia, which currently corresponds to a serum uric acid level of 7 mg / dL or higher in Japan. The method for measuring serum uric acid level is not particularly limited, but is preferably one used clinically, such as the uricase-peroxidase method (uricase-POD method).

[0021] In this specification, "risk allele" refers to an allele that constitutes a homozygous type in which the average serum uric acid level is higher than that of another homozygous type when the average serum uric acid level is calculated and compared in a population having two types of homozygous types at an SNP (Single Nucleotide Polymorphism) site.For example, when there are three genotypes, A / A, A / T, and T / T, in a certain SNP, if the average serum uric acid level of a group of people with A / A type is higher than that of a group of people with T / T type, the A allele that constitutes the A / A genotype with a higher average serum uric acid level is called a risk allele.The risk allele is also an allele that can be used as an indicator of a higher risk of a subject's serum uric acid level showing a high level after menopause when the risk allele exists in a certain SNP, for example, SNPs (a) to (c), compared to when other alleles (non-risk alleles) exist.

[0022] The single nucleotide polymorphisms (SNPs) (a) to (c) are as follows: (a) rs1351879 on human chromosome 2 (b) rs4430896 on human chromosome 2 (c) rs117377116 on human chromosome 12

[0023] Details of the above SNPs (a) to (c) are shown in Table 1 below. In this specification, the above SNPs (a) to (c) may be abbreviated as "SNP(a)," "SNP(b)," and "SNP(c)," respectively.

[0024] As will be described in Example 1 below, the above SNPs (a) to (c) are as follows. The above SNP (a) is rs1351879 on the human chromosomal region 2p24.1, and its alleles are A / G, with A being the risk allele and G being the non-risk allele. The above SNP (b) is rs4430896 on the human chromosomal region 2p24.1, and its alleles are A / G, with G being the risk allele and A being the non-risk allele. The above SNP (c) is rs117377116 on human chromosome region 12q22, and its alleles are A / G, with A being the risk allele and G being the non-risk allele.

[0025] The association of SNPs (a) to (c) with serum uric acid levels was not previously known, and this is a new finding in the present invention. Furthermore, it is not easy to infer the mechanism by which the SNP sites act on serum uric acid levels from the annotations published in the database for the SNP sites. However, as described in detail in Example 1, the present invention has confirmed that the SNP sites are correlated with serum uric acid levels in GWAS analysis of a population including adult men and women, and it is presumed that the SNP sites are involved in serum uric acid levels, although the mechanism is not yet clear.

[0026] Furthermore, hyperuricemia is much more prevalent in men than in women, and previous findings on genetic factors related to serum uric acid levels have been obtained using data from mostly men. On the other hand, as described in detail in Example 1, the present invention was discovered from a novel perspective of comparing premenopausal and postmenopausal adult female populations. It is known that serum uric acid levels in adult women tend to increase with the decrease in female hormones (estrogen) associated with menopause. However, sufficient knowledge has not been previously obtained about which factors are particularly likely to increase serum uric acid levels in certain populations. Clinically, hyperuricemia is known to cause not only gout but also vascular endothelial dysfunction, which increases the risk of cerebrovascular and cardiovascular disorders. The risk alleles newly identified in the present invention that cause significantly higher serum uric acid levels in postmenopausal populations compared to premenopausal populations may also have high application value in the medical industry.

[0027] In order to determine whether or not a subject has a genetic predisposition to high serum uric acid levels after menopause, the subject is preferably an adult woman who has not yet shown high serum uric acid levels after menopause and / or is a premenopausal woman at the time of determination. However, the subject is not necessarily limited to such adult women, and may also include, for example, postmenopausal women who have not yet measured their serum uric acid levels, even though they would show high serum uric acid levels if measured, and who are unaware of or do not know about the condition themselves or related parties. In such cases, it is expected that, for example, determining that a subject has a genetic predisposition to high serum uric acid levels after menopause using the method of the first aspect of the present invention may serve as an opportunity to discover that the subject has hyperuricemia.

[0028] The subject-derived nucleic acid is not particularly limited and may be, for example, a nucleic acid extract from a biological sample or biological specimen collected from the subject. The biological sample or biological specimen is not particularly limited as long as nucleic acid can be obtained from the biological sample or biological specimen, and examples thereof include body fluid samples such as blood, serum, saliva, sputum, sweat, tears, semen, and cerebrospinal fluid; mucosal exfoliation samples such as buccal cells and cheek swabs; lacrimal gland secretions; and body tissue samples such as tissue specimens.

[0029] The method of the first aspect of the present invention may include a detection step of detecting at least one allele of the single nucleotide polymorphisms (SNPs) (a) to (c). When the method includes the detection step, specifically, the allele of at least one of the SNPs (a) to (c) can be determined based on the detection result obtained by the detection step, and preferably, it can further determine whether or not at least one of the SNPs (a) to (c) is a risk allele.

[0030] At least one allele of the above single nucleotide polymorphisms (SNPs) (a) to (c) can be detected by scanning probe and nanopore DNA sequencing, pyrosequencing, denaturing gradient gel electrophoresis (DGGE), time-temperature gradient electrophoresis (TTGE), Zn(II)-cyclen polyacrylamide gel electrophoresis, homogeneous fluorescent PCR-based single nucleotide polymorphism analysis, phosphate-affinity polyacrylamide gel electrophoresis, high-throughput SNP genotyping platforms, molecular beacons, 5' nuclease reactions, Taqman assays, MassArray (single-base primer extension coupled with matrix-assisted laser desorption / ionization time-of-flight mass spectrometry), trityl mass tags, and genotyping platforms (Invader Assay (registered trademark), etc.), single base primer extension (SBE) assay, PCR amplification (e.g., PCR amplification on magnetic nanoparticles (MNPs)), restriction enzyme analysis of PCR products (RFLP method), allele-specific PCR, multi-primer extension (MPEX), isothermal smart amplification, PCR-SSCP (single-stranded conformation polymorphism analysis), sequencing, ARMS (Amplification Refracting Mutation System), and RNAse A cleavage method. For example, the detection may be by typing (genotyping) the genotype of one or more single nucleotide polymorphisms (SNPs) including at least one of the above SNPs (a) to (c).

[0031] The method of the first aspect of the present invention may be for determining whether or not a person is at risk of exhibiting high serum uric acid levels after menopause, before or at an early stage of the onset of hyperuricemia and / or a disease or condition associated with hyperuricemia.

[0032] Typical examples of the diseases or conditions associated with hyperuricemia include gout, gouty arthritis, cardiac or cerebrovascular disorders, myocardial infarction, kidney stones, urinary tract stones (including ureteral stones and bladder stones), decreased kidney function, chronic kidney disease, and renal failure, and may also be complications of these diseases or conditions, such as obesity, hypertension, dyslipidemia, and hyperglycemia.

[0033] That is, as described above, the method of the first aspect of the present invention is a method that can determine whether or not a subject is at risk of having a high serum uric acid level after menopause, depending on whether or not at least one of the single nucleotide polymorphisms (SNPs) (a) to (c) is a risk allele. Specifically, the presence or absence of at least one of the SNPs (a) to (c) can be used as an indicator of the risk of developing hyperuricemia after menopause and / or the risk that the subject will develop the above-mentioned diseases or conditions associated with hyperuricemia in the future (or may be the risk that the subject has developed the disease or condition at the time of determination).

[0034] The method of the first aspect of the present invention is suitable, for example, for detecting the risk of a subject for developing hyperuricemia and / or a disease or condition associated with hyperuricemia, for taking preventive measures to reduce the risk (including improving lifestyle habits and monitoring serum uric acid levels), for detecting hyperuricemia and / or a disease or condition associated with hyperuricemia in the subject, and / or for selecting a subject having hyperuricemia and / or a disease or condition associated with hyperuricemia.

[0035] By using the present invention, it is possible to predict, at an early stage, the risk of developing hyperuricemia after menopause in premenopausal women. In addition, since hyperuricemia also poses a risk of causing diseases such as heart disease and renal failure, the present invention can be used to take preventive measures to reduce the onset of hyperuricemia and the risk of associated diseases. As specific application examples in industrial use, for those determined to be likely to have an increased serum uric acid level after menopause, a system that recommends lifestyle habits that are less likely to develop known hyperuricemia since before menopause, a system that encourages regular monitoring of serum uric acid levels during menopause, etc. can be mentioned. These systems can also be incorporated into known genetic testing services.

[0036] <Method for Detecting the Presence or Absence of SNPs> A method for detecting at least one allele of the above single nucleotide polymorphisms (SNPs) (a) to (c) for use in the method of the first aspect of the present invention is also one of the present inventions and is the second aspect of the present invention. As a method for detecting at least one allele of the above single nucleotide polymorphisms (SNPs) (a) to (c), the detection step for detecting at least one allele of the above single nucleotide polymorphisms (SNPs) (a) to (c) described above for the method of the first aspect of the present invention, or the detection method in this step can be applied.

[0037] <Composition> The third aspect of the present invention is a composition for use in the method of the first aspect of the present invention, and the composition is a composition containing a reagent capable of directly or indirectly detecting at least one allele of the above single nucleotide polymorphisms (SNPs) (a) to (c).

[0038] The above reagent is not particularly limited as long as it can directly or indirectly detect at least one allele of the above single nucleotide polymorphisms (SNPs) (a) to (c). For example, known reagents can be used. For example, at least one selected from oligonucleotides, DNA probes, RNA probes, and ribozymes can be used.

[0039] <Kit> A fourth aspect of the present invention is a kit for use in the method of the first aspect of the present invention, the kit comprising a reagent capable of directly or indirectly detecting at least one allele of the single nucleotide polymorphisms (SNPs) (a) to (c) described above. The reagent may be any of those described above for the composition of the third aspect of the present invention. The kit is not particularly limited as long as it contains the reagent, and may be, for example, a DNA microarray, a DNA chip, a gene chip, or the like. [Example]

[0040] The present invention will be explained in more detail below with reference to examples, but the present invention is not limited to these examples.

[0041] Example 1 Tests and analysis were conducted on 642 healthy adult men and women (humans) according to the procedures outlined below. 1) Biological samples will be collected from the subjects and serum uric acid levels will be measured. 2) Extract the genome-derived DNA present in the subject's biological sample. 3) Detecting the alleles of single nucleotide polymorphisms (SNPs) contained in the above DNA. 4) The combination of the above SNP alleles will determine the type that will show high serum uric acid levels after menopause.

[0042] 1. Measurement of serum uric acid levels Blood samples were collected from the subjects and assayed using the uricase-peroxidase method (uricase POD method).

[0043] 2. Genotype Measurement Blood was collected from the subjects, and DNA was extracted and amplified according to standard methods. The DNA was then run on the "Japonica Array (registered trademark)" (array for gene polymorphism analysis, manufactured by Tohoku University Tohoku Medical Megabank Organization) to detect gene polymorphisms in each subject. The "Japonica Array (registered trademark)" is a gene polymorphism analysis array containing approximately 660,000 single nucleotide polymorphisms (SNPs), which was created based on the results of large-scale genome analysis of Japanese people.

[0044] 3. Identification of genotypes correlated with serum uric acid levels Quality control was performed on approximately 660,000 single nucleotide polymorphism (SNP) markers detected using the Japonica Array® genetic polymorphism analysis array. As quality control, SNPs with a genotyping success rate of less than 0.99 and a distorted Hardy-Weinberg equilibrium p-value (HWE: p<1.0×10) were selected. 6 ) and 14,703 SNPs with a minor allele frequency (MAF) of less than 0.01 were excluded for the association analysis. A total of 645,006 SNPs that passed quality control were analyzed for their association with serum uric acid levels using PLINK1.9 (http: / / pngu.mgh.harvard.edu / purcell / plink / ). As a result of the GWAS analysis, a total of 26 SNPs were found to be significant at the p<1.0×10 -5 ) and showed a significant correlation with serum uric acid levels.

[0045] 4. Identification of genetic factors that predispose adult women to elevated serum uric acid levels after menopause Of the 622 individuals used in the GWAS analysis, adult men and women for whom information on menopause was unavailable, as well as individuals with either the A / G or A / A genotype for the SNP (rs121907892) known to have the strongest correlation with serum uric acid levels among the SNPs identified in the above process, were excluded. The A allele of this SNP is a loss-of-function allele of the URAT1 / SLC22A12 gene, which is involved in uric acid reabsorption in the renal proximal tubules, and individuals with this allele have low serum uric acid levels (Gout and Nucleic Acid Metabolism, Vol. 42, Supplement (2018); https: / / www.jstage.jst.go.jp / article / gnam / 42 / Supplement / 42_suppl-26 / _pdf / -char / ja). The 215 premenopausal adult women and 211 postmenopausal adult women selected as a result of the exclusion were used to identify genetic predispositions that make serum uric acid levels more likely to increase after menopause in adult women from the following nine SNPs, which were not known to be associated with serum uric acid levels, among the SNPs identified in the above process.

[0046] [Table 1]

[0047] First, the mean serum uric acid levels in the population with each of the two homozygous types for each of the nine SNPs were calculated and compared. The allele that constitutes the homozygous type that shows a higher mean serum uric acid level than the other homozygous type is hereafter referred to as the risk allele.

[0048] Next, for each of the nine SNPs, a comparison was performed using two independent sample t-tests on the serum uric acid levels between those with and without the risk allele in both premenopausal and postmenopausal women, with a significance level set at 5%.

[0049] As a result, we were able to identify the following three SNPs where serum uric acid levels were significantly higher in postmenopausal women with the risk allele compared to those without the risk allele, while no significant difference was observed between those with and without the risk allele in premenopausal women. The analysis results of these three SNPs are shown in Figure 1. (a) SNP (rs1351879) in the human chromosome 2 region (b) SNP (rs4430896) in the human chromosome 2 region (c) SNP (rs117377116) in the human chromosome 12 region

[0050] 5. Discussion In this example, we demonstrated that at specific SNP locations (SNP (rs1351879) in the human chromosome 2 region, SNP (rs4430896) in the human chromosome 12 region, and SNP (rs117377116) in the human chromosome 12 region), there are alleles that result in significantly elevated mean serum uric acid levels only in postmenopausal women.

Claims

1. A method for determining whether or not there is a genetic predisposition to high serum uric acid levels after menopause, the method comprising: The method includes a step of determining that the subject has a genetic predisposition to postmenopausal high serum uric acid levels when at least one of the following single nucleotide polymorphisms (SNPs) (a) to (c) in a nucleic acid derived from an adult female subject is a risk allele, and determining that the subject does not have a genetic predisposition to postmenopausal high serum uric acid levels when none of the single nucleotide polymorphisms (SNPs) is a risk allele: The risk allele is an allele that constitutes a homozygous type whose average serum uric acid value is higher than that of the other homozygous type when average serum uric acid values ​​are calculated and compared in populations having two types of homozygous types, The method, wherein the high serum uric acid level and the high value for the serum uric acid level are serum uric acid levels of 7 mg / dL or higher. (a) rs1351879 on human chromosome 2 (b) rs4430896 on human chromosome 2 (c) rs117377116 on human chromosome 12 (however, The risk allele of the single nucleotide polymorphism (SNP) (a) is A, The risk allele of the single nucleotide polymorphism (SNP) (b) is G; The risk allele of the single nucleotide polymorphism (SNP) (c) is A.

2. The method of claim 1, wherein the subject is an adult female who has not yet shown high serum uric acid levels after menopause and / or is a premenopausal female at the time of assessment.

3. The method according to claim 1 or 2, which is used to determine whether or not there is a risk of showing high serum uric acid levels after menopause before or at an early stage of the onset of hyperuricemia and / or a disease or condition associated with hyperuricemia.

4. The method of claim 3, wherein the disease or condition associated with hyperuricemia is at least one selected from the group consisting of gout, gouty arthritis, cardiac or cerebrovascular disorders, myocardial infarction, kidney stones, urinary tract stones (including ureteral stones and bladder stones), decreased kidney function, chronic kidney disease, and renal failure.

5. The method according to any one of claims 1 to 4, which is used to detect the subject's risk of developing hyperuricemia and / or a disease or condition associated with hyperuricemia, to take preventive measures (including improving lifestyle habits and monitoring serum uric acid levels) to reduce the risk, to detect hyperuricemia and / or a disease or condition associated with hyperuricemia in the subject, and / or to select a subject having hyperuricemia and / or a disease or condition associated with hyperuricemia.

6. The method according to any one of claims 1 to 5, comprising a detection step of detecting at least one allele of the single nucleotide polymorphisms (SNPs) (a) to (c).

7. A method for detecting at least one allele of the single nucleotide polymorphisms (SNPs) (a) to (c), for use in the method according to any one of claims 1 to 6.

8. At least one allele of the single nucleotide polymorphisms (SNPs) (a) to (c) can be detected by scanning probe and nanopore DNA sequencing, pyrosequencing, denaturing gradient gel electrophoresis (DGGE), time-temperature gradient electrophoresis (TTGE), Zn(II)-cyclen polyacrylamide gel electrophoresis, homogeneous fluorescent PCR-based single nucleotide polymorphism analysis, phosphate-affinity polyacrylamide gel electrophoresis, high-throughput SNP genotyping platforms, molecular beacons, 5' nuclease reactions, Taqman assays, MassArray (single-base primer extension coupled with matrix-assisted laser desorption / ionization time-of-flight mass spectrometry), trityl mass tags, genotyping platforms (Invader 8. The method of claim 6 or 7, wherein the nucleotide sequence is detected by at least one technique selected from the group consisting of PCR amplification (e.g., PCR Amplification on Magnetic Nanoparticles (MNPs)), single base primer extension (SBE) assay, PCR amplification (e.g., PCR amplification on magnetic nanoparticles (MNPs)), restriction enzyme analysis of PCR products (RFLP method), allele-specific PCR, multiple primer extension (MPEX), isothermal smart amplification, PCR-SSCP (single-stranded conformation polymorphism analysis), sequencing, ARMS (Amplification Refracting Mutation System), and RNAse A cleavage method.

9. A composition for use in the method according to any one of claims 1 to 8, comprising a reagent capable of directly or indirectly detecting at least one allele of the single nucleotide polymorphisms (SNPs) (a) to (c).

10. A kit for use in the method according to any one of claims 1 to 8, comprising a reagent capable of directly or indirectly detecting at least one allele of the single nucleotide polymorphisms (SNPs) (a) to (c).

11. 11. The composition of claim 9 or the kit of claim 10, wherein the reagent is selected from an oligonucleotide, a DNA probe, an RNA probe, and a ribozyme.

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