PT  - JOURNAL ARTICLE
AU  - Saxena, Richa
AU  - Gianniny, Lauren
AU  - Burtt, Noël P.
AU  - Lyssenko, Valeriya
AU  - Giuducci, Candace
AU  - Sjögren, Marketa
AU  - Florez, Jose C.
AU  - Almgren, Peter
AU  - Isomaa, Bo
AU  - Orho-Melander, Marju
AU  - Lindblad, Ulf
AU  - Daly, Mark J.
AU  - Tuomi, Tiinamaija
AU  - Hirschhorn, Joel N.
AU  - Ardlie, Kristin G.
AU  - Groop, Leif C.
AU  - Altshuler, David
TI  - Common Single Nucleotide Polymorphisms in <em>TCF7L2</em> Are Reproducibly Associated With Type 2 Diabetes and Reduce the Insulin Response to Glucose in Nondiabetic Individuals
AID  - 10.2337/db06-0381
DP  - 2006 Oct 01
TA  - Diabetes
PG  - 2890--2895
VI  - 55
IP  - 10
4099  - http://diabetes.diabetesjournals.org/content/55/10/2890.short
4100  - http://diabetes.diabetesjournals.org/content/55/10/2890.full
SO  - Diabetes2006 Oct 01; 55
AB  - 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 × 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.