This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (10)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Exercise  • Obesity  • Genetics  • Genetic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

Evadnie Rampersaud, MSPH, PhD; Braxton D. Mitchell, PhD; Toni I. Pollin, PhD; Mao Fu, PhD; Haiqing Shen, PhD; Jeffery R. O’Connell, PhD; Julie L. Ducharme, MD; Scott Hines, MD; Paul Sack, MD; Rosalie Naglieri, MD; Alan R. Shuldiner, MD; Soren Snitker, MD, PhD

Arch Intern Med. 2008;168(16):1791-1797.

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; r² = 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.

Author Affiliations: Department of Medicine, University of Maryland (Drs Rampersaud, Mitchell, Pollin, Fu, Shen, O’Connell, Ducharme, Hines, Sack, Naglieri, Shuldiner, and Snitker), and the Geriatric Research and Education Clinical Center, Baltimore Veterans Administration Medical Center (Dr Shuldiner), Baltimore. Dr Rampersaud is now with the Miller School of Medicine, Miami Institute for Human Genetics, University of Miami, Miami, Florida.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

The FTO gene rs9939609 obesity-risk allele and loss of control over eating
Tanofsky-Kraff et al.
Am. J. Clin. Nutr. 2009;90:1483-1488.
ABSTRACT | FULL TEXT  

Life course variations in the associations between FTO and MC4R gene variants and body size
Hardy et al.
Hum Mol Genet 2009;0:ddp504v2-ddp504.
ABSTRACT | FULL TEXT  

Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity
Sonestedt et al.
Am. J. Clin. Nutr. 2009;90:1418-1425.
ABSTRACT | FULL TEXT  

Genetic Effects of FTO and MC4R Polymorphisms on Body Mass in Constitutional Types
Cha et al.
Evid Based Complement Alternat Med 2009;0:nep162v1-nep162.
ABSTRACT | FULL TEXT  

Modification effects of physical activity and protein intake on heritability of body size and composition
Silventoinen et al.
Am. J. Clin. Nutr. 2009;90:1096-1103.
ABSTRACT | FULL TEXT  

Physical activity attenuates the body mass index-increasing influence of genetic variation in the FTO gene
Vimaleswaran et al.
Am. J. Clin. Nutr. 2009;90:425-428.
ABSTRACT | FULL TEXT  

Childhood obesity: are genetic differences involved?
Bouchard
Am. J. Clin. Nutr. 2009;89:1494S-1501S.
ABSTRACT | FULL TEXT  

FTO Genotype Is Associated with Body Mass Index after the Age of Seven Years But Not with Energy Intake or Leisure-Time Physical Activity
Hakanen et al.
J. Clin. Endocrinol. Metab. 2009;94:1281-1287.
ABSTRACT | FULL TEXT