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

Summary, in English

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.

• Författare: Richa Saxena; Lauren Gianniny; Noel 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 Groop; David Altshuler
• Avdelning/ar: Translationell Muskel Forskning
• Publiceringsår: 2006
• Språk: Engelska
• Sidor: 2890-2895
• Publikation/Tidskrift/Serie: Diabetes
• Volym: 55
• Issue: 10
• Länkar: http://dx.doi.org/10.2337/db06-0381
• Dokumenttyp: Artikel i tidskrift
• Förlag: American Diabetes Association Inc.
• Ämne: Endocrinology and Diabetes
• Status: Published
• Forskningsgrupp: Genomics, Diabetes and Endocrinology
• ISBN/ISSN/Övrigt: ISSN: 1939-327X