Neuropeptide Y Promoter Variant rs16147 (-399 T/C) Is Associated With Susceptibility to Polycystic Ovary Syndrome

Background Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder with complex genetic and neuroendocrine underpinnings. Neuropeptide Y (NPY), a key regulator of energy balance and reproductive function, has been implicated in hypothalamic-pituitary-ovarian (HPO) axis dysregulation. However, data on variants of the NPY gene in PCOS remain limited. This study investigated the association between the NPY promoter variant rs16147 (-399 T/C) and susceptibility to PCOS. Methods In this case-control study, 102 women diagnosed with PCOS according to the Rotterdam criteria and 102 age-matched healthy controls were enrolled. Genomic DNA was extracted from peripheral blood samples, and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Demographic and anthropometric characteristics were recorded, and hormonal and metabolic parameters, including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, thyroid-stimulating hormone (TSH), total testosterone, fasting glucose, insulin levels, lipid profile components, and homeostasis model assessment of insulin resistance (HOMA-IR), were evaluated. Genotype-phenotype associations were also explored. Results Genotype and allele distributions differed significantly between groups. The CT genotype was detected in 84 women with PCOS (82.4%) compared to 24 controls (23.5%) and was associated with increased susceptibility to PCOS (odds ratio {OR} = 15.1; 95% confidence interval {CI}: 7.65-30.0; p < 0.001). In contrast, the CC genotype was more frequent in controls (78, 76.5%) than in the PCOS group (18, 17.6%). The TT genotype was not observed in either group. Similarly, the T allele was more prevalent in women with PCOS (84, 41.2%) than in controls (24, 11.8%) (OR = 5.25; 95% CI: 3.15-8.73; p < 0.001). No significant associations were observed between rs16147 genotypes and hormonal or metabolic parameters within the PCOS cohort. Conclusions The NPY promoter variant rs16147, particularly the CT genotype and T allele, may contribute to genetic susceptibility to PCOS rather than to clinical phenotype severity. However, these findings should be interpreted with caution and require validation in larger, multicenter populations.