FTO Genotype, Physical Activity and Coronary Heart Disease Risk in Swedish Men and Women
Background—Variants in the Fat mass and obesity-associated gene (FTO) predisposing to obesity and diabetes, have also been associated with cardiovascular disease. Physical activity has been suggested to attenuate the FTO effect on obesity, but it is unknown whether this is also true for cardiovascular disease. Therefore, we explored whether physical activity modifies the FTO association with coronary heart disease (CHD).
Methods and Results—FTO rs9939609 (T>A) polymorphism was genotyped in two Swedish population-based case-control studies with 1743 CHD cases and 4402 population controls (25-74 years, 41% women). Leisure time physical activity was assessed by questionnaires and three levels were defined: low, medium and high. Overall, carriers of the FTO A allele had an increased risk of CHD (OR 1.20, 95% CI 1.06-1.37) adjusted for age, sex, study and BMI. While A allele carriers with low physical activity had the highest CHD risk (OR 3.30, 95% CI 2.44-4.46) compared to those with TT genotype and high activity, the effects of FTO genotype and physical activity on CHD risk were approximately additive, indicating the absence of additive interaction. The stratum-specific relative risks of CHD from the A allele in subjects with low, medium and high physical activity, were OR 1.11 (95% CI 0.77-1.60), 1.22 (1.04-1.44) and 1.38 (1.06-1.80), respectively, but the suggested multiplicative interaction was not significant.
Conclusions—FTO rs9939609 A allele carriers have an increased CHD risk, and the association is not counteracted by increased physical activity.
- Received December 3, 2012.
- Revision received February 19, 2014.
- Accepted February 25, 2014.