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Diabetes DOI:10.2337/db06-0381

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

Publication TypeJournal Article
Year of Publication2006
AuthorsSaxena, R, Gianniny, L, Burtt, NP, Lyssenko, V, Giuducci, C, Sjögren, M, Florez, JC, Almgren, P, Isomaa, B, Orho-Melander, M, Lindblad, U, Daly, MJ, Tuomi, T, Hirschhorn, JN, Ardlie, KG, Groop, LC, Altshuler, D
Date Published2006/10/01

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.