Common Single Nucleotide Polymorphisms in TCF7L2 Are Reproducibly Associated With Type 2 Diabetes and Reduce the Insulin Response to Glucose in Nondiabetic Individuals-Reference-Cited by-同舟云学术

Common Single Nucleotide Polymorphisms in TCF7L2 Are Reproducibly Associated With Type 2 Diabetes and Reduce the Insulin Response to Glucose in Nondiabetic Individuals

Published:2006-10-01 Issue:10 Volume:55 Page:2890-2895
ISSN:0012-1797
Container-title:Diabetes
language:en
Short-container-title:

Author:

Saxena Richa¹²³,Gianniny Lauren¹,Burtt Noël P.¹,Lyssenko Valeriya⁴,Giuducci Candace¹,Sjögren Marketa⁴,Florez Jose C.¹²⁵,Almgren Peter⁴,Isomaa Bo⁶,Orho-Melander Marju⁴,Lindblad Ulf⁴⁷,Daly Mark J.¹²⁵,Tuomi Tiinamaija⁶,Hirschhorn Joel N.¹⁵⁸,Ardlie Kristin G.¹⁹,Groop Leif C.⁴⁶,Altshuler David¹²³⁵

Affiliation:

1. Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts

2. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts

3. Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts

4. Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Malmö, Lund University, Malmö, Sweden

5. Department of Medicine, Harvard Medical School, Boston, Massachusetts

6. Department of Medicine, Helsinki University Central Hospital, Folkhalsan Genetic Institute, Folkhalsan Research Center and Research Program for Molecular Medicine, University of Helsinki, Helsinki, Finland

7. Skaraborg Institute, Skövde, Sweden

8. Divisions of Genetics and Endocrinology, Children’s Hospital, Boston, Massachusetts

9. Genomics Collaborative, Cambridge, Massachusetts

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 × 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.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

Link

https://journals.org/diabetes/diabetes/article-pdf/55/10/2890/339958/zdb01006002890.pdf

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