目的:是人类男性生育性状的四个候选基因座(rs7867029,rs7174015,rs12870438和rs724078),在美国Hutterite种群的全基因组关联研究(GWAS)中鉴定,
结论:rs7867029,rs7174015和rs12870438与日本男性不育风险显著相关.
背景:最近,美国Hutterite人群的GWAS显示,41个单核苷酸多态性(SNP)与家庭规模或出生率显着相关。其中,在来自芝加哥的不同种族男性中,发现四个SNP(rs7867029,rs7174015,rs12870438和rs724078)与精液参数相关。
方法:这是一项病例对照关联研究,共有917名日本受试者,包括791个有生育能力的男人,无精子症76例,少精子症50例。
方法:根据精液分析(射精中没有精子)诊断为无精子症,血清激素水平和体检。少精子症定义为精子浓度<20×10(6)/ml。我们排除了任何已知原因导致不孕症的患者(即阻塞性无精子症,精索静脉曲张,隐睾,低促性腺激素性性腺功能减退,核型异常或AZFa完全缺失,b或c)。使用来自外周血样品的DNA和限制性片段长度多态性PCR或TaqMan探针对SNPrs7867029、rs7174015、rs12870438和rs724078进行基因分型。在三种不同的比较模型(加性,隐性或显性)。
结果:在可育对照中,所有四个SNP的基因型均处于Hardy-Weinberg平衡。SNPsrs7867029和rs7174015与少精子症相关[rs7867029:比值比(OR)=1.70,95%置信区间(CI)=1.07-2.68,P=0.024(对数相加);rs7174015:OR=6.52,95%CI=1.57-27.10,P=0.001.1287038,rsexinnigal-P=在校正多次测试后,显性模型下rs7174015与少精子症之间的关联以及加性和隐性模型下rs12870438与无精子症之间的关联仍然存在。rs724078与无精子症或少精子症之间没有关联。
结论:即使病例受试者的样本量不是很大,在日本人群中,我们发现3个SNP与男性不育风险相关.
结论:三个与不育相关的SNP可能有助于精子发生的数量减少。
背景:这项研究得到了日本厚生省(1013201)(至T.I.)的部分支持,科学研究资助(C)(23510242)(至A.Ta。)来自日本科学促进会,欧盟(BMH4-CT96-0314)(至T.I.)和武田科学基金会(至A.Ta.).没有任何作者有任何竞争的利益声明。
OBJECTIVE: Are the four candidate loci (rs7867029, rs7174015, rs12870438 and rs724078) for human male fertility traits, identified in a genome-wide association study (GWAS) of a Hutterite population in the USA, associated with male infertility in a Japanese population?
CONCLUSIONS: rs7867029, rs7174015 and rs12870438 are significantly associated with the risk of male infertility in a Japanese population.
BACKGROUND: Recently, a GWAS of a Hutterite population in the USA revealed that 41 single-nucleotide polymorphisms (SNPs) were significantly correlated with family size or birth rate. Of these, four SNPs (rs7867029, rs7174015, rs12870438 and rs724078) were found to be associated with semen parameters in ethnically diverse men from Chicago.
METHODS: This is a case-control association study in a total of 917 Japanese subjects, including 791 fertile men, 76 patients with azoospermia and 50 patients with oligozoospermia.
METHODS: Azoospermia was diagnosed on the basis of semen analysis (the absence of sperm in ejaculate), serum hormone levels and physical examinations. Oligozoospermia was defined as a sperm concentration of <20 × 10(6)/ml. We excluded patients with any known cause of infertility (i.e. obstructive azoospermia, varicocele, cryptorchidism, hypogonadotropic hypogonadism, karyotype abnormalities or complete deletion of AZF a, b or c). The SNPs rs7867029, rs7174015, rs12870438 and rs724078 were genotyped using DNA from peripheral blood samples and either restriction fragment length polymorphism PCR or TaqMan probes. Genetic associations between the four SNPs and male infertility were assessed using a logistic regression analysis under three different comparative models (additive, recessive or dominant).
RESULTS: The genotypes of all four SNPs were in Hardy-Weinberg equilibrium in the fertile controls. The SNPs rs7867029 and rs7174015 are associated with oligozoospermia [rs7867029: odds ratio (OR) = 1.70, 95% confidence interval (CI) = 1.07-2.68, P = 0.024 (log-additive); rs7174015: OR = 6.52, 95% CI = 1.57-27.10, P = 0.0099 (dominant)] and rs12870438 is associated with azoospermia (OR = 10.90, 95% CI = 2.67-44.60, P = 0.00087 (recessive)] and oligozoospermia [OR = 8.54, 95% CI = 1.52-47.90, P = 0.015 (recessive)]. The association between rs7174015 and oligozoospermia under a dominant model and between rs12870438 and azoospermia under additive and recessive models remained after correction for multiple testing. There were no associations between rs724078 and azoospermia or oligozoospermia.
CONCLUSIONS: Even though the sample size of case subjects was not very large, we found that three SNPs were associated with the risk of male infertility in a Japanese population.
CONCLUSIONS: The three infertility-associated SNPs may be contributing to a quantitative reduction in spermatogenesis.
BACKGROUND: This study was supported in part by the Ministry of Health and Welfare of Japan (1013201) (to T.I.), Grant-in-Aids for Scientific Research (C) (23510242) (to A.Ta.) from the Japan Society for the Promotion of Science, the European Union (BMH4-CT96-0314) (to T. I.) and the Takeda Science Foundation (to A.Ta.). None of the authors has any competing interests to declare.