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Assessing gene-trea...
Assessing gene-treatment interactions at the FTO and INSIG2 loci on obesity-related traits in the Diabetes Prevention Program
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- Franks, Paul W (författare)
- Umeå universitet,Medicin,Diabetes Prevention Program Coordinating Center, The Biostatistics Center, George Washington University, 6110 Executive Blvd, Suite 750, Rockville, MD 20852, USA
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Jablonski, KA (författare)
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Delahanty, LM (författare)
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McAteer, JB (författare)
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Kahn, SE (författare)
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Knowler, WC (författare)
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Florez, JC (författare)
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(creator_code:org_t)
- 2008-10-07
- 2008
- Engelska.
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Ingår i: Diabetologia. - New York : Springer. - 0012-186X .- 1432-0428. ; 51:12, s. 2214-2223
- Relaterad länk:
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https://link.springe...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- AIMS/HYPOTHESIS: The single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity associated gene (FTO) and the rs7566605 SNP located 10 kb upstream of the insulin-induced gene 2 gene (INSIG2) have been proposed as risk factors for common obesity.METHODS: We tested for genotype-treatment interactions on changes in obesity-related traits in the Diabetes Prevention Program (DPP). The DPP is a randomised controlled trial of 3,548 high-risk individuals from 27 participating centres throughout the USA who were originally randomised to receive metformin, troglitazone, intensive lifestyle modification or placebo to prevent the development of type 2 diabetes. Measures of adiposity from computed tomography were available in a subsample (n = 908). This report focuses on the baseline and 1 year results.RESULTS: The minor A allele at FTO rs9939609 was positively associated with baseline BMI (p = 0.003), but not with baseline adiposity or the change at 1 year in any anthropometric trait. For the INSIG2 rs7566605 genotype, the minor C allele was associated with more subcutaneous adiposity (second and third lumbar vertebrae [L2/3]) at baseline (p = 0.04). During follow-up, CC homozygotes lost more weight than G allele carriers (p = 0.009). In an additive model, we observed nominally significant gene-lifestyle interactions on weight change (p = 0.02) and subcutaneous (L2/3 [p = 0.01] and L4/5 [p = 0.03]) and visceral (L2/3 [p = 0.02]) adipose areas. No statistical evidence of association with physical activity energy expenditure or energy intake was observed for either genotype.CONCLUSIONS/INTERPRETATION: Within the DPP study population, common variants in FTO and INSIG2 are nominally associated with quantitative measures of obesity, directly and possibly by interacting with metformin or lifestyle intervention.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Adiposity
- Diabetes Prevention Program
- FTO
- Gene-environment interaction
- Genetic
- INSIG2
- Lifestyle
- Metformin
- Obesity
- Randomised controlled trial
- Troglitazone
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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