The FTO gene modifies weight, fat mass and insulin sensitivity in women with polycystic ovary syndrome, where its role may be larger than in other phenotypes

Abstract Aim Genome-wide association studies have shown that variation in the FTO gene predisposes to obesity and related traits that are common features of polycystic ovary syndrome (PCOS). The aim of the present study was to assess the effect of FTO variation on obesity, insulin sensitivity, and metabolic and hormonal profiles in PCOS. Methods We examined 136 PCOS women (mean body mass index [BMI]: 28.28 ± 6.95 kg/m2 , mean age: 25.36 ± 5.48 years). Anthropometric measurement, euglycaemic–hyperinsulinaemic clamp and oral glucose tolerance tests and sex hormone assessments were performed. The study group was genotyped for the FTO rs9939609 polymorphism. Results BMI (29.0 ± 6.9 kg/m2 vs 26.1 ± 6.8 kg/m2 ; P = 0.023), body weight (80.1 ± 20.7 kg vs 72.6 ± 20.2 kg; P = 0.048), fat mass (29.7 ± 1 6.6 kg vs 24.6 ± 17.7 kg; P = 0.045) and waist circumference (89.8 ± 16.7 cm vs 83.2 ± 17.1 cm; P = 0.028) were higher in carriers of at least one copy of the A allele. Differences in these parameters were more significant when comparing AA and TT homozygotes. Women with the AA genotype also had decreased insulin sensitivity ( P = 0.025) and follicle-stimulating hormone ( P = 0.036). In logistic-regression analyses, the association of the FTO gene polymorphism with insulin sensitivity was no longer significant when BMI was included in the model. Conclusion Variation in the FTO gene modifies weight, adiposity and other measures of obesity and insulin sensitivity in PCOS. The examined FTO gene variant appears to have a greater impact on obesity and related traits in PCOS than in other phenotypes. The effect on insulin sensitivity appears to be secondary to its influence on obesity and body fat.