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Physical Activity and the Association of Common FTO Gene Variants With Body Mass Index and Obesity

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Rampersaud, Evadnie, Mitchell, Braxton D., Pollin, Toni I., Fu, Mao, Shen, Haiqing, O’Connell, Jeffery R., Ducharme, Julie L., Hines, Scott, Sack, Paul, Naglieri, Rosalie, Shuldiner, Alan R., Snitker, Soren·2008·Archives of Internal Medicine

DOI 10.1001/archinte.168.16.1791PMC PMC3635949

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Abstract

BACKGROUND: Common FTO (fat mass and obesity associated) gene variants have recently been associated with body mass index (BMI) and obesity in several large studies. The role of lifestyle factors (such as physical activity) in those with an underlying FTO genetic predisposition is unknown. METHODS: To determine if FTO variants are associated with BMI in Old Order Amish (OOA) individuals, and to further determine whether the detrimental associations of FTO gene variants can be lessened by increased physical activity, a total of 704 healthy OOA adults were selected from the Heredity and Phenotype Intervention (HAPI) Heart Study, an investigation of gene x environment interactions in cardiovascular disease, for whom objective quantified physical activity measurements were available and for whom 92 single-nucleotide polymorphisms (SNPs) in FTO were genotyped. RESULTS: Twenty-six FTO SNPs were associated with BMI (P = .04 to <.001), including rs1477196 (P < .001) and rs1861868 (P < .001), 2 SNPs in moderate linkage disequilibrium in the OOA (D' = 0.82; r(2) = 0.36). Stratified analyses of rs1861868 revealed its association with BMI to be restricted entirely to those subjects with low sex- and age-adjusted physical activity scores (P < .001); in contrast, the SNP had no effect on those with above-average physical activity scores (P = .29), with the genotype x physical activity interaction achieving statistical significance (P = .01). Similar evidence for interaction was also obtained for rs1477196. CONCLUSIONS: Our results strongly suggest that the increased risk of obesity owing to genetic susceptibility by FTO variants can be blunted through physical activity. These findings emphasize the important role of physical activity in public health efforts to combat obesity, particularly in genetically susceptible individuals.

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Authors: Rampersaud, E., Mitchell, B. D., Pollin, T. I., Fu, M., Shen, H., O’Connell, J. R., Ducharme, J. L., Hines, S., Sack, P., Naglieri, R., Shuldiner, A. R., & Snitker, S.
Affiliations: University of Maryland, Baltimore (US)
ORCID: Rampersaud, Evadnie
Mitchell, Braxton D.
Pollin, Toni I.
Shen, Haiqing
Sack, Paul
Shuldiner, Alan R.
Venue: Archives of Internal Medicine
Publisher: American Medical Association (AMA)
Published: 2008-09-08
Volume: 168
Issue: 16
Pages: 1791
ISSN: 0003-9926 (ISSN-L)
DOI: 10.1001/archinte.168.16.1791
PMC: PMC3635949
OpenAlex: W2010505352
Cited by: 299
References: 31
Citations by year: 2026: 6 · 2025: 4 · 2024: 11 · 2023: 7 · 2022: 8 · 2021: 9 · 2020: 14 · 2019: 6 · 2018: 7 · 2017: 15 · 2016: 23 · 2015: 12 · 2014: 13 · 2013: 24 · 2012: 30
FWCI: 20.90
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Archives of Internal Medicine (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Heart, Lung, and Blood Institute (T32HL072751, U01HL072515)
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK072488)
National Center for Research Resources (M01RR016500, M01RR000052, M01RR 16500)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
Keywords: FTO, fat mass and obesity-associated gene, single nucleotide polymorphisms, body mass index, obesity, physical activity, gene-environment interaction, genetic susceptibility, Old Order Amish, linkage disequilibrium, cardiovascular disease
MeSH terms: Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Adult, Female, Genotype, Humans, Male, Middle Aged, Motor Activity, Obesity, Proteins, Risk Factors, Body Mass Index, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide

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Physical Activity and the Association of Common FTO Gene Variants With Body Mass Index and Obesity

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