鉴定 YAP1 为多囊卵巢综合征的一个新的易感基因。

Identification of YAP1 as a novel susceptibility gene for polycystic ovary syndrome.

机构信息

Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, Jinan, China.

出版信息

J Med Genet. 2012 Apr;49(4):254-7. doi: 10.1136/jmedgenet-2011-100727.

DOI:10.1136/jmedgenet-2011-100727

PMID:22499345

Abstract

BACKGROUND

A previously reported genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in Han Chinese found that several loci of p value around 10e-5 warrant investigation. Replication of the GWAS was applied in this study to determine whether gene YAP1 (yeast associated protein 1) is associated with PCOS.

METHODS

An independent set of 1115 PCOS patients and 1137 controls were recruited; single nucleotide polymorphisms (SNPs) rs11225138, rs11225161, and rs11225166 from YAP1 were selected for the replication study. Real-time quantitative PCR was applied for genotyping by TaqMan-MGB probe assay.

RESULTS

Meta-analysis showed that the allele frequency of rs11225161 (A/G) was significantly different between PCOS and controls at a GWA significance (Pmeta =3.98e-09). Genotype-phenotype correlation study found 30 min and 60 min glucose of the oral glucose tolerance test were higher in PCOS patients with rs11225161 risk allele A. The G allele of SNP rs11225138 (G/C) was a further risk factor for higher luteinising hormone level in PCOS patients (p=0.041).

CONCLUSION

YAP1 appears to be a new susceptibility gene for PCOS in Han Chinese women.

摘要

背景

一项先前针对多囊卵巢综合征（PCOS）的汉族人群全基因组关联研究（GWAS）发现，几个 p 值在 10e-5 左右的位点值得进一步研究。本研究应用 GWAS 复制来确定 YAP1（酵母相关蛋白 1）基因是否与 PCOS 相关。

方法

本研究纳入了 1115 名 PCOS 患者和 1137 名对照者的独立样本；选择 YAP1 中的单核苷酸多态性（SNP）rs11225138、rs11225161 和 rs11225166 进行复制研究。采用 TaqMan-MGB 探针法进行实时定量 PCR 基因分型。

结果

Meta 分析显示，在全基因组关联显著性水平（Pmeta=3.98e-09）下，rs11225161（A/G）等位基因频率在 PCOS 患者与对照组之间存在显著差异。基因型-表型相关性研究发现，携带 rs11225161 风险等位基因 A 的 PCOS 患者的口服葡萄糖耐量试验 30 分钟和 60 分钟血糖更高。SNP rs11225138（G/C）的 G 等位基因是 PCOS 患者黄体生成素水平升高的另一个危险因素（p=0.041）。