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

In English

Författare

  • 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
Visa allt

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.

Publiceringsår

2007

Språk

Engelska

Sidor

1209-1217

Publikation/Tidskrift/Serie

Diabetologia

Volym

50

Issue

6

Dokumenttyp

Artikel i tidskrift

Förlag

Springer

Ämne

  • Endocrinology and Diabetes

Nyckelord

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

Status

Published

Forskningsgrupp

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

ISBN/ISSN/Övrigt

  • ISSN: 1432-0428