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Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals

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Author

  • Richa Saxena
  • Lauren Gianniny
  • Noel P. Burtt
  • Valeriya Lyssenko
  • Candace Giuducci
  • Marketa Sjögren
  • Jose C. Florez
  • Peter Almgren
  • Bo Isomaa
  • Marju Orho-Melander
  • Ulf Lindblad
  • Mark J. Daly
  • Tiinamaija Tuomi
  • Joel N. Hirschhorn
  • Kristin G. Ardlie
  • Leif Groop
  • David Altshuler
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Summary, in English

Recently, common noncoding variants in the TCF7L2 gene were strongly associated with increased risk of type 2 diabetes in samples from Iceland, Denmark, and the U.S. We genotyped 13 single nucleotide polymorphisms (SNPs) across TCF7L2 in 8,310 individuals in family-based and case-control designs from Scandinavia, Poland, and the U.S. We convincingly confirmed the previous association of TCF7L2 SNPs with the risk of type 2 diabetes (rs7903146T odds ratio 1.40 [95% CI 1.30-1.50], P = 6.74 x 10(-20)). In nondiabetic individuals, the risk genotypes were associated with a substantial reduction in the insulinogenic index derived from an oral glucose tolerance test (risk allele homozygotes have half the insulin response to glucose of noncarriers, P = 0.003) but not with increased insulin resistance. These results suggest that TCF7L2 variants may act through insulin secretion to increase the risk of type 2 diabetes.

Publishing year

2006

Language

English

Pages

2890-2895

Publication/Series

Diabetes

Volume

55

Issue

10

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1939-327X