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

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.

• Authors: Richa Saxena, Lauren Gianniny, Noël P Burtt, Valeriya Lyssenko, Candace Giuducci, Marketa Sjögren, Jose C Florez, Peter Almgren, Bo Isomaa, Marju Orho-Melander, Ulf Lindblad, Mark J Daly, Tiinamaija Tuomi, Joel N Hirschhorn, Kristin G Ardlie, Leif C Groop, David Altshuler
• Journal: Diabetes (Diabetes) Vol. 55 Issue 10 Pg. 2890-5 (Oct 2006) ISSN: 0012-1797 [Print] United States
• PMID: 17003358 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• TCF Transcription Factors
• TCF7L2 protein, human
• Transcription Factor 7-Like 2 Protein
• Glucose

Topics

• Case-Control Studies
• Diabetes Mellitus, Type 2 (genetics)
• Glucose (pharmacology)
• Humans
• Insulin (physiology)
• Insulin Resistance (genetics)
• Polymorphism, Single Nucleotide
• Risk
• TCF Transcription Factors (genetics)
• Transcription Factor 7-Like 2 Protein