Association of TGFA gene polymorphisms (rs11466297 and rs3732248) with polycystic ovary syndrome (PCOS): a case-control study

Abstract

Polycystic ovary syndrome (PCOS) is a complicated endocrine condition that causes ovarian dysfunction, metabolic problems, and hormonal irregularities. Genetic factors profoundly affect its pathogenesis. This study investigates the association between polymorphisms in the Transforming Growth Factor Alpha (TGFA) gene, specifically rs11466297 and rs3732248, and the risk of PCOS. We conducted a case-control study involving 200 individuals confirmed to have PCOS and 200 control subjects. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Amplification Refractory Mutation System (ARMS-PCR) procedures to genotype the TGFA SNPs rs11466297 A/C and rs3732248 G/A. We performed statistical analyses, including odds ratios (OR) and 95% confidence intervals (CI), to evaluate the relationship between the polymorphisms and the risk of PCOS. Genotypic analysis revealed that the TGFA rs3732248 GA heterozygote was significantly associated with increased PCOS risk under the codominant model (OR = 2.16, 95% CI: 1.39–3.32, p < 0.001), dominant model (OR = 1.77, 95% CI: 1.18–2.65, p = 0.013), and overdominant model (OR = 2.26, 95% CI: 1.47–3.45, p = 0.001). All associations remained significant after Bonferroni correction (p < 0.025). For rs11466297, no significant association survived correction. PCOS patients had significantly higher BMI, waist circumference, total cholesterol, and triglycerides compared to controls (p < 0.001 for all). Haplotype analysis revealed no significant association between TGFA haplotypes and PCOS risk. This study is the first to demonstrate that the TGFA rs3732248 polymorphism is significantly associated with PCOS susceptibility in an Iranian population. These findings provide novel genetic evidence supporting a role for TGFA in PCOS pathogenesis and warrant replication in larger independent cohorts.