Genetic Variants of Steroidogenesis and Gonadotropin Pathways and Polycystic Ovary Syndrome Susceptibility: A Systematic Review and Meta-analysis.

Genetic variants are predisposing factors to polycystic ovary syndrome (PCOS), a multifactorial condition that often gets triggered due to various environmental factors. The study investigates the association of the variants of genes that are involved in the steroidogenesis pathway or gonadotropin pathway with the risk of PCOS. Appropriate keywords for predetermined genes were used to search in PubMed, Google Scholar, Science Direct, and Central Cochrane Library up to January 11, 2023. PROSPERO (CRD42022275425). Inclusion criteria: (a) case-control study; (b) genotype or allelic data. Exclusion criteria were: (a) duplicate studies; (b) clinical trials, systematic reviews, meta-analysis or conference abstract, case reports; (c) other than the English language; (d) having insufficient data; e) genetic variants for which meta-analysis has been reported recently and does not have a scope of the update. Various genetic models were applied as per data availability. Overall 12 variants of 7 genes were selected for the analysis. Relevant data were extracted from 47 studies which include 10,584 PCOS subjects and 16,150 healthy controls. Meta-analysis indicates a significant association between TOX3 rs4784165 [ORs = 1.08, 95% CI (1.00-1.16)], HMGA2 rs2272046 [ORs = 2.73, 95% CI (1.97-3.78)], YAP1 rs1894116 [OR = 1.22, 95% CI (1.13-1.33)] and increased risk of PCOS. Whereas FSHR rs2268361 [ORs = 0.84, 95% CI (0.78-0.89)] is associated with decreased PCOS risk. When sensitivity analysis was carried out, the association became significant for CYP19 rs700519 and FSHR rs6165 under an additive model. In addition, C9Orf3 rs3802457 became significantly associated with decreased PCOS risk with the removal of one study. Insignificant association was observed for CYP19A (rs2470152), FSHR (rs2349415, rs6166), C9Orf3 (rs4385527), GnRH1 (rs6185) and risk of PCOS. Our findings suggest association of CYP19A (rs700519), TOX3 (rs4784165), HMGA2 (rs2272046), FSHR (rs6165, rs2268361), C9orf3 (rs3802457), and YAP1 (rs1894116) with risk for PCOS.