RESUMO
Polycystic ovary syndrome (PCOS) and type-2 diabetes mellitus (T2DM) share common genetic features. Transcription factor 7-like-2 (TCF7L2) is consistently studied T2DM susceptibility locus. However, limited studies on TCF7L2 have failed to demonstrate any link with the PCOS risk. Therefore, we investigated the association of TCF7L2 polymorphic variant (rs12255372) with the PCOS risk. We recruited 120 PCOS cases, diagnosed as per Rotterdam 2003 criteria, and an equal number of age-matched controls. Besides a detailed clinical assessment, subjects underwent biochemical and hormonal profiling. Genotyping for rs12255372 was done by PCR-RFLP. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs) of genotype-phenotype correlations. The PCOS cases reported fewer menstrual cycles per year and exhibited signs of hyperandrogenism. The heterozygous genotype of rs12255372 was strongly associated with the PCOS risk (OR = 2.00; 95%CI: 1.07-3.76). Unlike controls, only 3 cases harbored TT genotype, and the PCOS risk persisted in the dominant model (GT + TT) as well. Moreover, we found a synergistic effect modification by the variant genotype in the subjects who had family histories of T2DM, hirsutism, or menstrual irregularities. We report a significant association of the TCF7L2 polymorphic variant rs12255372 with the PCOS risk.
RESUMO
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.
