Association of FTO gene with hyperandrogenemia and metabolic parameters in women with polycystic ovary syndrome

Variants in the fat mass and obesity–associated gene (FTO) are associated with obesity and type 2 diabetes mellitus. Women with polycystic ovary syndrome (PCOS) are frequently affected by obesity and impaired glucose tolerance. The aim of this study was to investigate the impact of FTO variants (rs9939609) on metabolic and endocrine parameters in PCOS women. We genotyped the single nucleotide polymorphism rs9939609 (T/A) in 288 PCOS women and performed metabolic and hormonal measurements, oral glucose tolerance test, hirsutism score, and lipometry. The A/T + A/A genotype showed an increased prevalence in overweight/obese PCOS patients (odds ratio [OR] = 1.91, P = .028) and in PCOS women with impaired glucose tolerance (OR = 3.23, P = .009). The A allele was associated with a significant increase in free testosterone (P = .042), weight (P = .024), body mass index (P = .011), 2-hour glucose (P = .047), 1-hour insulin (P = .032), and AUCins (area under the curve insulin) (P = .038). In a logistic regression analysis, the A allele was associated with free testosterone (P = .025; OR = 1.54; 95% confidence interval, 1.06-2.25; B = 0.86). Total body fat (percentage) (P = .016), total fat mass (P = .013), visceral adipose tissue mass (P = .044), and subcutaneous fat mass (P = .011) were significantly increased in PCOS women carrying the A allele. We demonstrated that variants within the FTO gene influence hyperandrogenemia and anthropometric parameters in women with PCOS, indicating an important role of FTO variants not only in obesity and diabetes but also in hyperandrogenism in women with PCOS.