Effect modification of luteinizing hormone chorionic gonadotropin hormone receptor gene variant (rs2293275) on clinical and biochemical profile, and levels of luteinizing hormone in polycystic ovary syndrome patients

Abstract

Abstract Background Polycystic ovary syndrome (PCOS) is a common multifaceted endocrine disorder among reproductive women. Deranged luteinizing hormone levels and associated downstream signalling 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 inconclusive. We evaluated association of LHCGR rs2293275 polymorphic variant with PCOS risk and its impact on clinicobiochemical features of PCOS. Methods 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 (OR) at 95%confidence intervals (95%CIs). Results PCOS cases reported lower annual menstrual cyclicity, significantly higher BMI and Ferriman Galway score (p < 0.01). Levels of serum testosterone, TSH, FSH and indicators of glucose homeostasis were significantly deranged in cases than controls. Higher risk of developing PCOS was noted in GA (OR = 10.4, P < 0.0001) or AA (OR = 7.73, P = 0.02) genotype carriers and 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 T2DM (OR = 117;p < 0.0001) or hirsutism (OR = 79;p < 0.0001). We also found a significant linear increase in the serum LH levels in the subjects carrying GA and AA genotypes. Conclusion In the present study, we report a significant association ofthe LHCGR rs2293275 variant with the PCOS risk.