Thrombophilia-related gene variants may be linked to polycystic ovary syndrome susceptibility and its related traits

Abstract

Background Polycystic ovary syndrome (PCOS) is a prevalent endocrinopathy in reproductive-aged women having both gynecological and metabolic comorbidities. PCOS increases the risk of cardiovascular and thromboembolic diseases due to heightened prothrombotic states, suggesting shared genetic determinants with thrombophilia. In addition, convergence of these polymorphisms to insulin resistance, a hallmark feature of PCOS, may exacerbate PCOS risk and further intensify hypercoagulability-associated metabolic and reproductive manifestations.Methods This case-control study explores the association between MTHFR (C677T), FGB (-148C/T, -249C/T, -455G/A), FXIII (V34L), and FV (FVL, rs6020) and risk of PCOS development and its related traits in PCOS (n = 475) and control (n = 245) women. Clinical, biochemical, and hormonal parameters were estimated for all study participants and genotyping was carried out by direct sequencing.Results To the best of our knowledge, this is the first time that FGB promoter polymorphisms (-148C/T and -455G/A) were investigated and showed nominal association with reduced risk of PCOS prior to multiple testing correction. Additionally, potential genotype–phenotype trends with metabolic and hormonal parameters were noted in both controls and women with PCOS, with and without insulin resistance.Conclusion Genetic profiling of thrombophilia-related gene polymorphisms could help monitoring and management of PCOS and its related reproductive and metabolic complications.