Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals.
Authors | |
Keywords | |
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. |
Year of Publication | 2006
|
Journal | Diabetes
|
Volume | 55
|
Issue | 10
|
Pages | 2890-5
|
Date Published | 2006 Oct
|
ISSN | 0012-1797
|
URL | |
DOI | 10.2337/db06-0381
|
PubMed ID | 17003358
|
Links | |
Grant list | 1 K23 DK65978-03 / DK / NIDDK NIH HHS / United States
|