DataSheet_1_Analysis of HIF2α polymorphisms in infertile women with polycystic ovary syndrome or unexplained infertility.xlsx

ObjectiveTo evaluate HIF2α polymorphisms and glucose metabolism in a group of women with polycystic ovary syndrome (PCOS) or unexplained infertility (UI).
PatientsThe infertile group (n=148) consisted of 96 women with PCOS, 52 women with UI, and176 women without infertility as a healthy control group.
InterventionWe genotyped 29 single nucleotide polymorphisms (SNPs) of HIF2α by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based genotyping technology. The genetic associations were analyzed statistically.
Main outcome measuresAllele frequency, genotype distribution and haplotype analyze of the HIF2α polymorphisms were performed. Body mass index (BMI), waist circumference, uric acid (UA), high-sensitivity C-reactive protein (hsCRP), lipids, glucose and insulin tolerance - were also measured.
ResultsInfertile women with PCOS had a higherBMI and waist circumference, elevated hsCRP and uric acid (UA) levels, impaired glucose tolerance, and increased levels of plasma insulin compared to UI patients and healthy women. SNP analysis of HIF2α revealed that the allele and genotype frequencies of rs4953361 were significantly associated with infertile women with PCOS. Haplotype analysis of the HIF2α polymorphism identified haplotypes TGG and TGA as being associated with infertile women with PCOS. Women with the AA genotype of rs4953361 had a significantly higher BMI and post load plasma glucose and insulin levels than those of women with the GG genotype.
ConclusionInfertile women with PCOS more commonly have metabolic disturbances than those with UI. This is the first study to report an association between HIF2α polymorphisms (rs4953361) and the risk of infertile women with PCOS, not UI, in Han Chinese population. These results require replication in larger populations.
In this observational study, we did not report the results of a health care intervention on human participants. The study was approved by the Human Research Ethics Committee of the First Affiliated Hospital of Chongqing Medical University. Clinical data and peripheral blood samples were collected only after explaining the objectives of the study and obtaining a signed informed consent form.

研究目的：本研究旨在评估多囊卵巢综合征（PCOS）或不明原因不孕（UI）女性群体中，缺氧诱导因子2α（HIF2α）基因多态性与糖代谢的相关性。
研究对象：本研究纳入148例不孕女性，其中包括96例多囊卵巢综合征（PCOS）患者、52例不明原因不孕（UI）患者，另纳入176例非不孕健康女性作为健康对照组。
实验方法：采用基于基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）的基因分型技术，对缺氧诱导因子2α（HIF2α）的29个单核苷酸多态性（SNPs）位点进行基因分型，并开展遗传关联的统计学分析。
主要观察指标：对缺氧诱导因子2α（HIF2α）基因多态性的等位基因频率、基因型分布及单倍型进行分析；同时检测受试者的体重指数（BMI）、腰围、血尿酸（UA）、高敏C反应蛋白（hsCRP）、血脂水平、血糖及胰岛素耐量。
研究结果：与不明原因不孕（UI）患者及健康女性相比，合并多囊卵巢综合征（PCOS）的不孕女性体重指数（BMI）与腰围更高，血清高敏C反应蛋白（hsCRP）及血尿酸（UA）水平升高，葡萄糖耐量受损，血浆胰岛素水平亦显著升高。针对缺氧诱导因子2α（HIF2α）的单核苷酸多态性（SNPs）分析显示，rs4953361位点的等位基因及基因型频率与合并PCOS的不孕女性存在显著相关性。单倍型分析结果表明，HIF2α基因多态性的TGG与TGA单倍型与合并PCOS的不孕女性存在显著关联。携带rs4953361位点AA基因型的女性，其体重指数（BMI）、负荷后血糖及血浆胰岛素水平均显著高于携带GG基因型的女性。
研究结论：合并多囊卵巢综合征（PCOS）的不孕女性相较于不明原因不孕（UI）患者，更易出现代谢紊乱。本研究首次在汉族人群中报道了缺氧诱导因子2α（HIF2α）基因多态性（rs4953361）与合并PCOS的不孕女性患病风险的相关性，而非与不明原因不孕（UI）相关。上述研究结果需在更大规模人群中进行验证。
本研究为观察性研究，未报告针对人类受试者的医疗干预相关结果。本研究经重庆医科大学附属第一医院人体研究伦理委员会批准。所有受试者均在明确研究目的并签署书面知情同意书后，方可收集其临床数据及外周血样本。