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Diabetologia. 2008 Dec;51(12):2214-23. doi: 10.1007/s00125-008-1158-x. Epub 2008 Oct 7.

Assessing gene-treatment interactions at the FTO and INSIG2 loci on obesity-related traits in the Diabetes Prevention Program.

Author information

  • 1Genetic Epidemiology and Clinical Research Group, Department of Public Health and Clinical Medicine, Section for Medicine, Umeå University Hospital, Umeå, Sweden. paul.franks@medicin.umu.se

Erratum in

  • Diabetologia. 2009 Jul;52(7):1456.

Abstract

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.

PMID:
18839134
[PubMed - indexed for MEDLINE]
PMCID:
PMC2947367
Free PMC Article

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