Transcription factor TCF7L2 genetic study in the French population: expression in human beta-cells and adipose tissue and strong association with type 2 diabetes.
In: Diabetes, Jg. 55 (2006-10-01), Heft 10, S. 2903-8
academicJournal
Zugriff:
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 beta-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 beta-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.
Titel: |
Transcription factor TCF7L2 genetic study in the French population: expression in human beta-cells and adipose tissue and strong association with type 2 diabetes.
|
---|---|
Autor/in / Beteiligte Person: | Cauchi, S ; Meyre, D ; Dina, C ; Choquet, H ; Samson, C ; Gallina, S ; Balkau, B ; Charpentier, G ; Pattou, F ; Stetsyuk, V ; Scharfmann, R ; Staels, B ; Frühbeck, G ; Froguel, P |
Zeitschrift: | Diabetes, Jg. 55 (2006-10-01), Heft 10, S. 2903-8 |
Veröffentlichung: | Alexandria, VA : American Diabetes Association ; <i>Original Publication</i>: [New York, American Diabetes Association], 2006 |
Medientyp: | academicJournal |
ISSN: | 0012-1797 (print) |
DOI: | 10.2337/db06-0474 |
Schlagwort: |
|
Sonstiges: |
|