A Common Variant in the FTO Gene Is Associated with Obesity and Obesity Related Features in Women with Polycystic Ovary Syndrome
Abstract Number: 1740-P
Authors: IRINA KOWALSKA, MACIEJ T. MALECKI, MAREK STRACZKOWSKI, JAN SKUPIEN, MONIKA KARCZEWSKA-KUPCZEWSKA, AGNIESZKA NIKOLAJUK, AGNIESZKA ADAMSKA, MAGDALENA SZOPA, NATALIA WAWRUSIEWICZ-KURYLONEK, SLAWOMIR WOLCZYNSKI, JACEK SIERADZKI, MARIA GORSKA
Institutions: Bialystok, Poland, Krakow, Poland
Results: Genome wide association studies have shown that variation in the fat mass and obesity-associated (FTO) gene predisposes to obesity and related traits. Obesity and insulin resistance 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, metabolic and hormonal profile in a cohort of PCOS women . We examined 136 PCOS women (mean BMI- 28.28±6.95kg/m2, mean age - 25.36±5.48 years). Clinical examination, anthropometric measurements, euglycemic hyperinsulinemic clamp, OGTT, lipids and sex hormone assessments were performed. The FTO rs9939609 polymorphism was genotyped using the restriction fragment length polymorphism method. Obesity related parameters such as BMI (29.0±6.9 vs. 26.1±6.8 kg/m2, p=0.023), body weight (80.1±20.7 vs. 72.6±20.2kg, p=0.048), fat mass (29.7±16.6 vs. 24.6±17.7kg, p=0.045), and waist circumference (89.8±16.7 vs. 83.2±17.1cm, p=0.028) were higher in the carriers of at least one copy of the A allele (dominant model). The differences in these parameters were even more significant when we compared the AA and TT homozygotes. Women with AA genotype had larger BMI (p=0.014), body weight (p=0.020), fat mass (p=0.018), waist circumference (p=0.021) and decreased insulin sensitivity index (M) (4.4±2.5 vs. 5.9±1.1mg/kg/min, p=0.025). Individuals homozygous for the A allele at rs9939609 were at increased risk of being obese (OR = 4.51; 95% CI = 1.3 to 16.5, p = 0.016) compared with those homozygous for the low-risk T allele. In logistic regression analysis, the association of the FTO gene polymorphism with insulin sensitivity in the PCOS patients was no longer significant when BMI was included in the model. Our data show that the variation in the FTO gene is associated with BMI, other measures of obesity and insulin sensitivity in PCOS women. The effect on insulin sensitivity seems to be secondary to its influence on obesity. The examined FTO gene variant seems to have larger impact on the risk of obesity in this PCOS cohort than previously described in the general population, although this requires further confirmation.