Association of Vascular Endothelial Growth Factor A-2549 I/D polymorphism with polycystic ovary syndrome susceptibility in Turkish women.

OBJECTIVE: The aim of this case-control study was to evaluate whether the Vascular Endothelial Growth Factor A promoter rs35569394 (-2549 insertion/deletion) polymorphism is associated with polycystic ovary syndrome risk and related clinical-metabolic features.

METHODS: The study included 104 women with polycystic ovary syndrome diagnosed according to Rotterdam criteria and 128 controls. Clinical, hormonal, and metabolic variables were recorded, homeostatic model assessment of insulin resistance was calculated, and Vascular Endothelial Growth Factor A-2549 insertion/deletion genotypes were determined by direct polymerase chain reaction. Hardy-Weinberg equilibrium was assessed in controls. Benjamini-Hochberg false-discovery-rate-adjusted p-values were calculated for the 11 clinical comparisons, while prespecified Bonferroni-adjusted p-values were retained for genotype and family-history contrasts.

RESULTS: Body mass index, prolactin, homeostatic model assessment of insulin resistance, insulin, follicle stimulating hormone, luteinizing harmone, and total testosterone were higher in the polycystic ovary syndrome group. Overall genotype distribution differed between groups (Cramer's V=0.20; chi-square=8.87, p=0.012). The detection/deletion genotype was more frequent in polycystic ovary syndrome patients than controls (30.77% vs. 15.63%; Cohen's h=0.36; raw p=0.007; Bonferroni-adjusted p=0.028; OR 2.40, 95%CI 1.28-4.51). The family-history detection/deletion comparison did not remain significant after adjustment (raw p=0.018; adjusted p=0.072). Hardy-Weinberg equilibrium analysis in controls yielded an exact p-value of 0.050 and a Pearson p-value of 0.037.

CONCLUSION: In this Turkish case-control sample, the Vascular Endothelial Growth Factor A-2549 insertion/deletion detection/deletion genotype was more frequent among women with polycystic ovary syndrome than among controls. This observed association does not establish causality, a functional effect, phenotype-specific relevance, or clinical utility. Deviation from Hardy-Weinberg equilibrium in controls, residual confounding from incomplete matching, limited power, and lack of functional validation make the finding preliminary. Independent validation in larger, well-matched cohorts with prespecified genotyping quality control, phenotype stratification, and functional studies is required.