Department of Molecular Endocrinology, National Institute for Research in Reproductive Health, Mumbai, India.
Department of Clinical Research, National Institute for Research in Reproductive Health, Mumbai, India.
Gynecol Endocrinol. 2021 Aug;37(8):716-720. doi: 10.1080/09513590.2021.1906854. Epub 2021 Mar 27.
The aetiopathogenesis of the multigenic multifactorial endocrinopathy, polycystic ovary syndrome (PCOS) has been explored using linkage, candidate gene and genome-wide association studies. Contradictory reports of replication studies attributed to phenotypic, ethnic and geographic variations are available. In this study, we investigated the association of Han Chinese GWAS polymorphism (rs13429458) in thyroid adenoma-associated gene () with PCOS susceptibility and its related traits in Indian women.
We genotyped rs13429458 of by direct sequencing and investigated its association with PCOS and its related traits in controls ( = 150) and PCOS women ( = 348). All women were extensively phenotyped in terms of anthropometric, hormonal and metabolic parameters. Association of polymorphism with PCOS risk and its related traits was carried out by regression analysis.
Genotypic and allele frequencies for rs13429458 were not different between controls and PCOS. Women with PCOS carrying variant allele showed significantly reduced fasting glucose levels, and decreased free and bioavailable testosterone and free androgen index.
To our knowledge, this is the first study to demonstrate that although this polymorphism does not alter PCOS susceptibility, it favorably impacts glucose metabolism and hyperandrogenism in Indian women with PCOS only. This study highlights that genetic predisposition markers for PCOS may differ with ethnicity and phenotypic variations.
多基因多因素内分泌疾病多囊卵巢综合征（PCOS）的病因学已通过连锁、候选基因和全基因组关联研究进行了探索。关于复制研究的矛盾报告归因于表型、种族和地理变异。在这项研究中，我们调查了中国人 GWAS 多态性（rs13429458）在甲状腺腺瘤相关基因（）与印度女性 PCOS 易感性及其相关特征的关联。
我们通过直接测序对 rs13429458 进行基因分型，并在对照组（n=150）和 PCOS 女性（n=348）中研究其与 PCOS 及其相关特征的关联。所有女性均在人体测量、激素和代谢参数方面进行了广泛的表型分析。通过回归分析研究多态性与 PCOS 风险及其相关特征的关联。
rs13429458 的基因型和等位基因频率在对照组和 PCOS 组之间没有差异。携带变异等位基因的 PCOS 女性的空腹血糖水平显著降低，游离和生物可利用的睾酮和游离雄激素指数降低。
据我们所知，这是第一项研究表明，尽管该多态性不会改变 PCOS 的易感性，但它仅在印度患有 PCOS 的女性中有利地影响葡萄糖代谢和高雄激素血症。这项研究强调，PCOS 的遗传易感性标志物可能因种族和表型变异而有所不同。
