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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.
- Publication
Diabetes, 2006, Vol 55, Issue 10, p2890
- ISSN
0012-1797
- Publication type
Journal Article
- DOI
10.2337/db06-0381