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- Title
Common Single Nucleotide Polymorphisms in TCF7L2 Are Reproducibly Associated With Type 2 Diabetes and Reduce the Insulin Response to Glucose in Nondiabetic Individuals.
- Authors
Saxena, Richa; Gianniny, Lauren; Burtt, Noël P.; Lyssenko, Valeriya; Giuducci, Candace; Sjögren, Marketa; Florez, Jose C.; Almgren, Peter; Isomaa, Bo; Orho-Melander, Marju; Lindblad, Ulf; Daly, Mark J.; Tuomi, Tiinamaija; Hirschhorn, Joel N.; Ardlie, Kristin G.; Groop, Leif C.; Altshuler, David
- Abstract
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. Diabetes 55:2890-2895, 2006
- Subjects
TYPE 2 diabetes; DIABETES; GLUCOSE tolerance tests; GLUCOSE; INSULIN resistance; DIABETES complications
- Publication
Diabetes, 2006, Vol 55, Issue 10, p2890
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db06-0381