期刊
DIABETES
卷 60, 期 5, 页码 1637-1644出版社
AMER DIABETES ASSOC
DOI: 10.2337/db10-1340
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资金
- University of Bergen
- Haukeland University Hospital
- Helse Vest
- Innovest
- Research Council of Norway
- GlaxoSmithKline Norway
- Norwegian Diabetes Association
- Swedish Research Council [31475113580]
- European Foundation for the Study of Diabetes
- Novo Nordisk and Albert Pahlsson Foundations
- Linnaeus
- Knut and Alice Wallenberg Foundation
- Heart and Lung Foundation
- Diabetes Research Society
- Nordic Center of Excellence
- Lund University
- Pahlsson Foundation
- Craaford Foundation
- Novo Nordisk Foundation
- European Network of Genomic and Genetic Epidemiology
- Wallenberg Foundation
- Eli Lilly
- Novartis
OBJECTIVE-FTO is the most important polygene identified for obesity. We aimed to investigate whether a variant in FTO affects type 2 diabetes risk entirely through its effect on BMI and how FTO) influences BMI across adult life span. RESEARCH DESIGN AND METHODS-Through regression models, we assessed the relationship between the FTO single nucleotide polymorphisms rs9939609, type 2 diabetes, and BMI across life span in subjects from the Norwegian population-based HUNT study using cross-sectional and longitudinal perspectives. For replication and meta-analysis, we used data from the Malmo Diet and Cancer (MDC) and Malmo Preventive Project (MPP) cohorts, comprising a total sample of 41,504 Scandinavians. RESULTS-The meta-analysis revealed a highly significant association for rs9939609 with both type 2 diabetes (OR 1.13; P = 4.5 x 10(-8)) and the risk to develop incident type 2 diabetes (OR 1.16; P = 3.2 x 10(-8)). The associations remained also after correction for BMI and other anthropometric measures. Furthermore, we confirmed the strong effect on BMI (0.28 kg/m(2) per risk allele; P = 2.0 x 10(-26), with no heterogeneity between different age-groups. We found no differences in change of BMI over time according to rs9939609 risk alleles, neither overall (Delta BMI = 0.0 [-0.05, 0.05]) nor in any individual age stratum, indicating no further weight gain attributable to FTO genotype in adults. CONCLUSIONS-We have identified that a variant in FTO alters type 2 diabetes risk partly independent of its observed effect on BMI. The additional weight gain as a result of the FTO risk variant seems to occur before adulthood, and the BMI difference remains stable thereafter. Diabetes 60:1637-1644, 2011
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