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FTO, Type 2 Diabetes, and Weight Gain Throughout Adult Life A Meta-Analysis of 41,504 Subjects From the Scandinavian HUNT, MDC, and MPP Studies

Author:
  • Jens K. Hertel
  • Stefan Johansson
  • Emily Sonestedt
  • Anna Jonsson
  • Rolv T. Lie
  • Carl G. P. Platou
  • Peter Nilsson
  • Gull Rukh
  • Kristian Midthjell
  • Kristian Hveem
  • Olle Melander
  • Leif Groop
  • Valeriya Lyssenko
  • Anders Molven
  • Marju Orho-Melander
  • Pal R. Njolstad
Publishing year: 2011
Language: English
Pages: 1637-1644
Publication/Series: Diabetes
Volume: 60
Issue: 5
Document type: Journal article
Publisher: American Diabetes Association Inc.

Abstract english

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

Keywords

  • Endocrinology and Diabetes

Other

Published
  • Nutrition Epidemiology
  • Genomics, Diabetes and Endocrinology
  • Internal Medicine - Epidemiology
  • ISSN: 1939-327X
Emily Sonestedt
E-mail: emily [dot] sonestedt [at] med [dot] lu [dot] se

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