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- Title
Transcription Factor TCF7L2 Genetic Study in the French Population.
- Authors
Cauchi, Stéphane; Meyre, David; Dina, Christian; Choquet, Hélène; Samson, Chantal; Gallina, Sophie; Balkau, Beverley; Charpentier, Guillaume; Pattou, François; Stetsyuk, Volodymyr; Scharfmann, Raphaël; Staels, Bart; Frühbeck, Gema; Froguel, Philippe
- Abstract
Recently, the transcription factor 7-like 2 (TCF7L2) gene has been associated with type 2 diabetes in subjects of European origin in the DeCode study. We genotyped the two most associated variants (rs7903146 and rs12255372) in 2,367 French type 2 diabetic subjects and in 2,499 control subjects. Both the T-allele of rs7903146 and the T-allele of rs12255372 significantly increase type 2 diabetes risk with an allelic odds ratio (OR) of 1.69 (95% CI 1.55-1.83) (P = 6.0 x 10-35) and 1.60 (1.47-1.74) (P = 7.6 x 10-28), respectively. In nonobese type 2 diabetic subjects (BMI <30 kg/m², n = 1,346), the ORs increased to 1.89 (1.72-2.09) (P = 2.1 x 10-38) and 1.79 (1.62-1.97) (P = 5.7 x 10-31), respectively. The rs7903146 T at-risk allele associates with decreased BMI and earlier age at diagnosis in the type 2 diabetic subjects (P = 8.0 x 10-3 and P = 3.8 x 10-4, respectively), which is supported by quantitative family-based association tests. TCF7L2 is expressed in most human tissues, including mature pancreatic β-cells, with the exception of the skeletal muscle. In the subcutaneous and omental fat from obese type 2 diabetic subjects, TCF7L2 expression significantly decreased compared with obese normoglycemic individuals. During rat fetal β-cell differentiation, TCF7L2 expression pattern mimics the key marker NGN3 (neurogenin 3), suggesting a role in islet development. These data provide evidence that TCF7L2 is a major determinant of type 2 diabetes risk in European populations and suggests that this transcription factor plays a key role in glucose homeostasis. Diabetes 55: 2903-2908, 2006
- Subjects
TRANSCRIPTION factors; TYPE 2 diabetes; DIABETES; PANCREATIC beta cells; ISLANDS of Langerhans
- Publication
Diabetes, 2006, Vol 55, Issue 10, p2903
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db06-0474