Department of Life Sciences, Jaipur National University, Jaipur, India.
Departments of Endocrinology, Sheri Kashmir Institute of Medical Sciences, Srinagar, India.
Biochem Genet. 2023 Aug;61(4):1418-1432. doi: 10.1007/s10528-022-10327-z. Epub 2023 Jan 12.
Polycystic ovary syndrome (PCOS) is a common multifaceted endocrine disorder among reproductive-aged women. Deranged luteinizing hormone levels and associated downstream signaling cascade mediated by its receptor luteinizing hormone chorionic gonadotropin receptor (LHCGR) are pivotal in the etiopathogenesis of PCOS. Genetic variations in the LHCGR have been associated with PCOS risk. However, the results are mixed and inconclusive. We evaluated the association of the LHCGR rs2293275 polymorphic variant with PCOS risk and its association with clinico-biochemical features of PCOS. 120 confirmed PCOS cases and an equal number of age-matched controls were subjected to clinical, biochemical, and hormonal investigations. Genotyping for rs2293275 was performed using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression models were used to calculate odds ratios (ORs) at 95% confidence intervals (95% CIs). In the current study, PCOS cases reported a lower number of menstrual cycles per year than respective controls. A significantly higher BMI, Ferriman Galway score, levels of serum testosterone, insulin, TSH, FSH, and fasting glucose were observed in cases than in controls (p < 0.01). Compared to GG carriers, we observed a higher risk of developing PCOS in the subjects who harbored GA (OR 10.4, p < 0.0001) or AA (OR 7.73, p = 0.02) genotype. The risk persisted in the dominant model (GA + AA) as well (OR 10.29, p = 0.01). On stratification, a higher risk of developing PCOS was observed in variant genotype carriers who had a family history of either type two diabetes mellitus (OR 117; p < 0.0001) or hirsutism (OR 79; p < 0.0001). We also found significantly elevated levels of serum LH levels in the subject harboring GA and AA genotypes when compared to GG carriers. In the present study, we report a significant association of the LHCGR rs2293275 variant with the PCOS risk.
多囊卵巢综合征（PCOS）是一种常见的生殖期妇女多方面的内分泌紊乱。黄体生成素（LH）水平的紊乱及其受体黄体生成素促性腺激素受体（LHCGR）的下游信号级联反应在 PCOS 的发病机制中起着关键作用。LHCGR 的遗传变异与 PCOS 的风险有关。然而，结果是混杂的，没有定论。我们评估了 LHCGR rs2293275 多态性变体与 PCOS 风险的关系及其与 PCOS 的临床生化特征的关系。120 例确诊的 PCOS 病例和数量相等的年龄匹配对照者接受了临床、生化和激素调查。使用聚合酶链反应-限制性片段长度多态性对 rs2293275 进行基因分型。使用逻辑回归模型计算 95%置信区间（95%CI）的比值比（OR）。在本研究中，PCOS 病例报告的每年月经周期数低于相应的对照组。病例组的 BMI、Ferriman-Galway 评分、血清睾酮、胰岛素、TSH、FSH 和空腹血糖水平显著高于对照组（p<0.01）。与 GG 携带者相比，我们观察到携带 GA（OR 10.4，p<0.0001）或 AA（OR 7.73，p=0.02）基因型的受试者发生 PCOS 的风险更高。在显性模型（GA+AA）中也存在这种风险（OR 10.29，p=0.01）。分层分析显示，在携带变异基因型且有 2 型糖尿病（OR 117；p<0.0001）或多毛症（OR 79；p<0.0001）家族史的受试者中，发生 PCOS 的风险更高。我们还发现，与 GG 携带者相比，携带 GA 和 AA 基因型的受试者的血清 LH 水平显著升高。在本研究中，我们报告了 LHCGR rs2293275 变体与 PCOS 风险之间的显著关联。
