Characterizing Genetic, Epigenetic, Nutritional, and Clinico‐Biochemical Profile of Women With Polycystic Ovary Syndrome: A Case–Control Study

<b>Objectives:</b> Polycystic ovary syndrome (PCOS) is among the most frequently encountered endocrinopathies in women. This study aimed to characterize the genetic (<i>INSR, FTO, DENND1A</i>, and <i>Nrf2</i>) expressions and epigenetic (DNA methylation) modifications, nutritional, metabolic, inflammatory, and hormonal markers for patients with PCOS in comparison with their age-matched healthy controls. <b>Design & Methods:</b> The study also aimed to assess the genetic expressions concerning vitamin D status. Sixty-six patients with PCOS and 69 age-matched healthy controls were recruited. Fasting blood samples were used to measure genetic and biochemical variables. Real-time PCR was used to assess gene expressions, the bisulfite conversion method was used to evaluate DNA methylation, and multiplex immunoassays were used to measure inflammatory markers. <b>Results:</b> Only two genes (<i>INSR and FTO</i>) were significantly (<i>p</i> < 0.05) upregulated, while one gene (<i>Nrf2</i>) was significantly (<i>p</i> < 0.05) downregulated in cases in comparison with controls. Furthermore, cases showed significantly (<i>p</i> < 0.05) higher BMI (kg/m²), fat mass, visceral fat surface area, and body fat percentage, as well as higher serum triglyceride levels, atherogenic index, VLDL levels, and TC/HDL and TG/HDL ratios when compared to controls. In contrast, HDL levels were significantly lower (<i>p</i> < 0.05) in the cases. Inflammatory markers (<i>hs-</i>CRP, IL-1β, IL-6, TNF-α, and VEGF) were significantly (<i>p</i> < 0.05) higher, while anti-inflammatory markers (IL-2 and IL-10) were significantly lower in cases when compared to controls. <b>Conclusions:</b> Women with PCOS may have distinct genetic expressions and anthropometric, metabolic, and inflammatory markers that predispose to the progression of the disease. Identifying predictive biomarkers fosters the application of precision medicine and personalized nutrition approaches in preventing and managing PCOS.