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

Journal article
Authors Jaana Gustavsson
Kirsten Mehlig
Karin Leander
Lauren Lissner
Lena Björck
Annika Rosengren
Fredrik Nyberg
Published in Circulation: Cardiovascular Genetics
Volume 7
Issue 2
Pages 171-177
ISSN 1942-325X
Publication year 2014
Published at Institute of Medicine, School of Public Health and Community Medicine
Institute of Medicine, Department of Public Health and Community Medicine, Section of Occupational and environmental medicine
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 171-177
Language en
Keywords coronary disease, molecular epidemiology, motor activity
Subject categories Molecular medicine (genetics and pathology), Clinical Medicine


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.)

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