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Association testing of common variants in the insulin receptor substrate-1 gene (IRS1) with type 2 diabetes

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Author

  • J. C. Florez
  • Marketa Sjögren
  • C. M. Agapakis
  • N. P. Burtt
  • Peter Almgren
  • Ulf Lindblad
  • Göran Berglund
  • T. Tuomi
  • D. Gaudet
  • M. J. Daly
  • K. G. Ardlie
  • J. N. Hirschhorn
  • D. Altshuler
  • Leif Groop
Show all

Summary, in English

Aims/hypothesis Activation of the insulin receptor substrate-1 (IRS1) is a key initial step in the insulin signalling pathway. Despite several reports of association of the G972R polymorphism in its gene IRS1 with type 2 diabetes, we and others have not observed this association in well-powered samples. However, other nearby variants might account for the putative association signal. Subjects and methods We characterised the haplotype map of IRS1 and selected 20 markers designed to capture common variations in the region. We genotyped this comprehensive set of markers in several family-based and case-control samples of European descent totalling 12,129 subjects. Results In an initial sample of 2,235 North American and Polish case-control pairs, the minor allele of the rs934167 polymorphism showed nominal evidence of association with type 2 diabetes (odds ratio [OR] 1.25, 95% CI 1.03-1.51, p=0.03). This association showed a trend in the same direction in 7,659 Scandinavian samples (OR 1.16, 95% CI 0.96-1.39, p=0.059). The combined OR was 1.20 (p=0.008), but statistical correction for the number of variants examined yielded a p value of 0.086. We detected no differences across rs934167 genotypes in insulin-related quantitative traits. Conclusion/interpretation Our data do not support an association of common variants in IRS1 with type 2 diabetes in populations of European descent.

Publishing year

2007

Language

English

Pages

1209-1217

Publication/Series

Diabetologia

Volume

50

Issue

6

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • SNP
  • type 2 diabetes
  • common variants
  • insulin resistance
  • IRS1
  • disequilibrium
  • linkage
  • single nucleotide polymorphism
  • genetic association

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Cardiovascular Research - Hypertension
  • Community Medicine
  • Family Medicine and Community Medicine
  • Internal Medicine - Epidemiology

ISBN/ISSN/Other

  • ISSN: 1432-0428