Genetic variation in exon 17 of INSR is associated with insulin resistance and hyperandrogenemia among lean Indian women with polycystic ovary syndrome
Genetic variation in exon 17 of INSR is associated with insulin resistance and hyperandrogenemia among lean Indian women with polycystic ovary syndrome
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DOI：
10.1530/eje-08-0932
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发表时间：
2009-05-01
影响因子：
5.8
通讯作者：
Maitra, Anurupa
中科院分区：
文献类型：
--
作者：
Mukherjee, Srabani;Shaikh, Nuzhat;Maitra, Anurupa
目的：多囊卵巢综合征（PCOS）是一种多基因疾病，胰岛素抵抗是其标志性特征之一。据报道，胰岛素受体（INSR）基因外显子 17 的多态性与 PCOS 相关。我们调查了印度女性的这种关联及其与多囊卵巢综合症相关特征的假定关系。方法：在本病例对照研究中，通过直接测序对 180 名 PCOS 女性和 144 名年龄匹配的对照者进行多态性调查。临床、人体测量。还估计了生化和激素参数。结果：INSR 外显子 17 中 His1058 的沉默 C/T 多态性被发现存在于我们的研究人群中。多态性基因型（CT+TT）与瘦女性PCOS显着相关（chi(2)=8.493。df=1，P=0.004）。它与较高的空腹胰岛素水平相关（P=0.02）。胰岛素抵抗的稳态模型评估（P=0.005）。游离雄激素指数（P=0.03）。瘦 PCOS 女性的定量胰岛素敏感性检查指数较低（P=0.004）。在该队列中，外显子 17 中没有发现其他新的或已知的多态性。结论：研究表明，INSR 的 His1058 的 C/T 多态性与瘦印度女性而非肥胖印度女性中的 PCOS 存在显着相关性。在同一组中也发现其与胰岛素抵抗和高雄激素血症指数的相关性。这些发现强化了这样的观念：瘦女性和肥胖女性的 PCOS 发病机制不同。
Objective: Polycystic ovary syndrome (PCOS) is a multigenic disorder, and insulin resistance is one of its hallmark features. Polymorphisms in exon 17 of insulin receptor (INSR) gene are reported to be associated with PCOS. We investigated this association in Indian women and its putative relationship with PCOS associated traits. which has not been explored so far.Methods: In this case control Study the polymorphisms were investigated by direct sequencing in 180 women with PCOS and 144 age matched controls. Clinical, anthropometric. biochemical, and hormonal parameters were also estimated.Results: The silent C/T polymorphism at His1058 in exon 17 of INSR Was found to be present in our study Population. The polymorphic genotype (CT+TT) was significantly associated with PCOS in lean women, (chi(2) =8.493. df=1, P=0.004). It showed association with higher fasting insulin levels (P=0.02). homeostasis model assessment of insulin resistance (P=0.005). free androgen index (P=0.03). and lower quantitative insulin sensitivity check index (P=0.004) in lean PCOS women. No other novel or known polymorphism was identified in exon 17 in this cohort.Conclusions: The study shows significant association of C/T polymorphism at His1058 of INSR with PCOS in the lean rather than obese Indian women. Its association with indices of insulin resistance and hyperandrogenemia is also seen in the same group. The findings strengthen the concept that pathogenesis of PCOS is different in lean and obese women.