Low Physical Activity Accentuates the Effect of the FTO rs9939609 Polymorphism on Body Fat Accumulation
Open accessAbstract
OBJECTIVE—Three independent studies have shown that variation in the fat mass and obesity-associated (FTO) gene associates with BMI and obesity. In the present study, the effect of FTO variation on metabolic traits including obesity, type 2 diabetes, and related quantitative phenotypes was examined. RESEARCH DESIGN AND METHODS—The FTO rs9939609 polymorphism was genotyped in a total of 17,508 Danes from five different study groups. RESULTS—In studies of 3,856 type 2 diabetic case subjects and 4,861 normal glucose-tolerant control subjects, the minor A-allele of rs9939609 associated with type 2 diabetes (odds ratio 1.13 [95% CI 1.06–1.20], P = 9 × 10−5). This association was abolished when adjusting for BMI (1.06 [0.97–1.16], P = 0.2). Among 17,162 middle-aged Danes, the A-allele associated with overweight (1.19 [1.13–1.24], P = 1 × 10−12) and obesity (1.27 [1.20–1.34], P = 2 × 10−16). Furthermore, obesity-related quantitative traits such as body weight, waist circumference, fat mass, and fasting serum leptin levels were significantly elevated in A-allele carriers. An interaction between the FTO rs9939609 genotype and physical activity (P = 0.007) was found, where physically inactive homozygous risk A-allele carriers had a 1.95 ± 0.3 kg/m2 increase in BMI compared with homozygous T-allele carriers. CONCLUSIONS—We validate that variation in FTO is associated with type 2 diabetes when not adjusted for BMI and with an overall increase in body fat mass. Furthermore, low physical activity seems to accentuate the effect of FTO rs9939609 on body fat accumulation.
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Physically inactive homozygous risk A-allele carriers in rs9939609 had a 2 kg/m2 greater BMI compared with homozygous T-allele carriers in a cross-sectional study of 17,000 Danes.
“Physically inactive homozygous risk A-allele in rs9939609 carriers had a 2 kg/m2 greater BMI compared with homozygous T-allele carriers in a cross-sectional study of 17,000 Danes (14).”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [14]
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- Authors
- Andreasen, C. H., Stender-Petersen, K. L., Mogensen, M. S., Torekov, S. S., Wegner, L., Andersen, G., Nielsen, A. L., Albrechtsen, A., Borch-Johnsen, K., Rasmussen, S. S., Clausen, J. O., Sandbæk, A., Lauritzen, T., Hansen, L., Jørgensen, T., Pedersen, O., & Hansen, T.
- Affiliations
- Steno Diabetes Center, Gentofte, Denmark
- University of Copenhagen (DK)
- Aarhus University (DK)
- Novo Nordisk (Denmark) (DK)
- Glostrup Hospital (DK)
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2008-01-01
- Volume
- 57
- Issue
- 1
- Pages
- 95-101
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2166884301
- Cited by
- 476
- References
- 18
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 9 · 2023: 13 · 2022: 8 · 2021: 12 · 2020: 13 · 2019: 22 · 2018: 21 · 2017: 27 · 2016: 28 · 2015: 20 · 2014: 31 · 2013: 28 · 2012: 37
- FWCI
- 27.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Velux Stiftung
- Strategiske Forskningsråd (2101-06-0005)
- Sundhed og Sygdom, Det Frie Forskningsråd
- European Commission (LSHM‐CT‐2005‐018734)
- A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal
- Diabetesforeningen
- Medical Research Council
- Fonden til Lægevidenskabens Fremme
- 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, rs9939609 polymorphism, type 2 diabetes, obesity, body fat accumulation, physical activity, gene-environment interaction, body mass index, waist circumference, fat mass, leptin, genetic susceptibility
- MeSH terms
- Adipose Tissue, Adult, Denmark, Diabetes Mellitus, Type 2, Female, Genotype, Humans, Oxo-Acid-Lyases, Male, Middle Aged, Motor Activity, Obesity, Polymorphism, Genetic, Reference Values, Genetic Variation, Linkage Disequilibrium, Body Mass Index, Odds Ratio, Glucose Intolerance
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