Possible Association of Three Polymorphisms in Cytokine TNF-a (238G/A, 308G/A, 1031T/C) with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

Background: Polycystic ovarian syndrome (PCOS) cases have recently increased drastically among women during ovulation. The etiology of this endocrine disorder remains complex due to its multiple links that affect women of all ethnicities and races. Recent studies have implicated tumor necrosis factor-alpha (TNF-α) in PCOS pathophysiology. This study examines the associations of TNF-α polymorphisms 238G/A, 308G/A, and 1031T/C with PCOS. Methods: We searched the Google Scholar, PubMed, EMBASE, Scopus, and Science Citation Index databases to identify suitable case-control studies and literature reviews for the statistical analysis. The obtained data were evaluated using the Review Manager 5.4 software. An odds ratio and 95% confidence interval were calculated for each genetic model. Results: Twenty-three studies met the eligibility criteria, comprising 3294 cases and 3288 controls. Meta-analysis showed no significant association between TNF-α polymorphisms 238G/A and 308G/A and PCOS risk. However, TNF-α polymorphism 1031T/C was significantly associated with PCOS risk. Conclusion: This meta-analysis indicates that TNF-α polymorphisms 238G/A and 308G/A may not be associated with PCOS risk, while TNF-α polymorphism 1031T/C appears associated with PCOS risk. However, a larger sample size is required to evaluate this association.