Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Fertil Steril. 2013 May;99(6):1774-8. doi: 10.1016/j.fertnstert.2012.12.033. Epub 2013 Jan 30.
To replicate variants in candidate genes associated with polycystic ovary syndrome (PCOS) in a population of European women with PCOS and control subjects.
Case-control association analysis and meta-analysis.
Major academic hospital.
PATIENT(S): Women of European ancestry with PCOS (n = 525) and controls (n = 472), aged 18-45 years.
INTERVENTION(S): Variants previously associated with PCOS in candidate gene studies were genotyped (n = 39). Metabolic, reproductive, and anthropomorphic parameters were examined as a function of the candidate variants. All genetic association analyses were adjusted for age, body mass index, and ancestry and were reported after correction for multiple testing.
MAIN OUTCOME MEASURE(S): Association of candidate gene variants with PCOS.
RESULT(S): Three variants, rs3797179 (SRD5A1), rs12473543 (POMC), and rs1501299 (ADIPOQ), were nominally associated with PCOS. However, they did not remain significant after correction for multiple testing, and none of the variants replicated in a sufficiently powered meta-analysis. Variants in the FBN3 gene (rs17202517 and rs73503752) were associated with smaller waist circumferences, and variant rs727428 in the SHBG gene was associated with lower sex hormone-binding globulin levels.
CONCLUSION(S): Previously identified variants in candidate genes do not seem to be associated with PCOS risk.
NCT00166569.
在多囊卵巢综合征（PCOS）的欧洲女性患者和对照者中，复制候选基因中与 PCOS 相关的变异。
病例对照关联分析和荟萃分析。
主要学术医院。
欧洲血统的 PCOS 患者（n=525）和对照者（n=472），年龄 18-45 岁。
对先前候选基因研究中与 PCOS 相关的变异进行基因分型（n=39）。作为候选变异的函数，检查代谢、生殖和人体测量参数。所有遗传关联分析均根据年龄、体重指数和种族进行调整，并在经过多次测试校正后报告。
候选基因变异与 PCOS 的关联。
三个候选基因变异 rs3797179（SRD5A1）、rs12473543（POMC）和 rs1501299（ADIPOQ）与 PCOS 具有名义相关性。然而，在经过多次测试校正后，它们不再具有统计学意义，并且没有一个变异在充分有效的荟萃分析中得到复制。FBN3 基因（rs17202517 和 rs73503752）中的变异与腰围较小有关，而 SHBG 基因中的 rs727428 变异与较低的性激素结合球蛋白水平有关。
先前在候选基因中鉴定的变异似乎与 PCOS 风险无关。
NCT00166569。
