Title of study: Genotypic and metabolic implications of tumor necrosis factor-α (TNF-α) −1031 (T/C) polymorphism in Kashmiri women with polycystic ovary syndrome (PCOS): a case–control study

Abstract Background Polycystic ovary syndrome (PCOS) is a chronic inflammatory disease characterized by a hyperandrogenic state, irregular menses, and polycystic ovaries (PCO). Tumor necrosis factor-alpha (TNF-α), a key pro-inflammatory cytokine, plays a significant role in this process of inflammation. Studying TNF-α polymorphisms is important as genetic variations may influence TNF-α expression, potentially affecting individual susceptibility to disease and its severity. The −1031 (T > C) single-nucleotide polymorphism (SNP) in the TNF-α has been linked to inflammatory and metabolic disorders, but its association with PCOS, particularly in Kashmiri population, is not well explored. Objectives The objective of the study was to assess the impact of −1031 (T > C) SNP in the TNF-α on the vulnerability of PCOS in women from Kashmir and to find out its correlation with clinical, hormonal, and metabolic parameters. Methods This study enrolled 210 PCOS patients and 203 age and body mass index (BMI) matched healthy controls. Genotyping of −1031 (T > C) SNP was performed using the restriction fragment length polymorphism (RFLP) method. Biochemical, hormonal, and metabolic profiles were investigated. The study primarily employed Chi-square tests, t tests, and ANOVA. Results TC genotype was significantly more frequent in PCOS cases (43.8%) vs. controls (21.6%) [odds ratio (OR) = 2.81; 95% confidence interval (CI) 1.83–4.33; p = 0.001)]. The C allele frequency was higher in cases (21.9%) vs. controls (10.83%) (OR = 2.30; 95% CI 1.56–3.40; p = 0.001). TC genotype carriers showed higher fasting insulin, homeostasis model assessment insulin resistance index (HOMA-IR), triglyceride levels, and reduced quantitative insulin sensitivity check index (QUICKI), indicating insulin resistance (IR) ( p < 0.05). Conclusion The −1031 (T > C) SNP in the TNF-α gene is significantly associated with increased susceptibility to PCOS in Kashmiri women, with the TC genotype linked to higher insulin resistance and adverse metabolic parameters.