FTO Genotype, Physical Activity, and Coronary Heart Disease Risk in Swedish Men and Women

Abstract

Background-Variants in the fat mass-and obesity-associated gene (FTO) predisposing to obesity and diabetes mellitus 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 2 Swedish population-based case-control studies with 1743 CHD cases and 4402 population controls (25-74 years of age; 41% women). Leisure time physical activity was assessed by questionnaires, and 3 levels were defined: low, medium, and high. Overall, carriers of the FTO A allele had an increased risk of CHD (odds ratio, 1.20; 95% confidence interval, 1.06-1.37) adjusted for age, sex, study, and body mass index. Although A-allele carriers with low physical activity had the highest CHD risk (odds ratio, 3.30; 95% confidence interval, 2.44-4.46) compared with 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 odds ratio 1.11 (95% confidence interval, 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. (Circ Cardiovasc Genet. 2014;7:171-177.)

Relationships between <em>FTO</em> rs9939609, <em>MC4R</em> rs17782313, and <em>PPAR&gamma;</em> rs1801282 polymorphisms and the occurrence of selected metabolic and hormonal disorders in middle-aged and elderly men &ndash; a preliminary study

“…Zavatarri et al51 showed no association between the FTO rs9939609 polymorphism and the parameters of lipid metabolism and stressed that AA homozygotes are particularly predisposed to obesity. Population studies conducted by Gustavsson et al52 on Gothenburg residents confirmed that AA and TA genotypes have a greater WC and a higher BMI compared to TT genotype.…”

Effect of FTO rs9930506 on obesity and interaction of the gene variants with dietary protein and vitamin E on C‐reactive protein levels in multi‐ethnic Malaysian adults

“…Gustavsson et al . found that the minor allele of the FTO gene was associated with higher proportion of subjects with overweight and obesity. They also reported that there was no association of FTO genotypes with blood lipids and physical activity levels.…”

Effect of six type II diabetes susceptibility loci and an FTO variant on obesity in Pakistani subjects

“…This SNP is known to predispose to obesity, type II diabetes and cardiovascular diseases and has also been linked to psychological disorders. [55][56][57][58] A longitudinal study in Brazil found a 0.07 kg/m 2 /year weight gain for each additional risk allele. 59 It has been previously reported that the overall risk of obesity is increased~1.3-fold per risk allele.…”