Journal of Molecular Medicine

, Volume 85, Issue 7, pp 777–782

TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis

Authors

  • Stéphane Cauchi
    • CNRS, 8090, Institute of BiologyPasteur Institute
  • Younes El Achhab
    • Laboratory of EpidemiologyFaculty of Medicine and Pharmacy of Fez
  • Hélène Choquet
    • CNRS, 8090, Institute of BiologyPasteur Institute
  • Christian Dina
    • CNRS, 8090, Institute of BiologyPasteur Institute
  • Franz Krempler
    • Department of Internal MedicineKrankenhaus Hallein
  • Raimund Weitgasser
    • Department of Internal MedicineParacelsus Medical University and Landeskliniken Salzburg
  • Chakib Nejjari
    • Laboratory of EpidemiologyFaculty of Medicine and Pharmacy of Fez
  • Wolfgang Patsch
    • Department of Laboratory MedicineParacelsus Medical University and Landeskrankenhaus Salzburg
  • Mohamed Chikri
    • Laboratory of BiochemistryFaculty of Medicine and Pharmacy of Fez
  • David Meyre
    • CNRS, 8090, Institute of BiologyPasteur Institute
    • CNRS, 8090, Institute of BiologyPasteur Institute
    • Section of Genomic Medicine, Imperial College LondonHammersmith Hospital
Rapid Communication

DOI: 10.1007/s00109-007-0203-4

Cite this article as:
Cauchi, S., El Achhab, Y., Choquet, H. et al. J Mol Med (2007) 85: 777. doi:10.1007/s00109-007-0203-4

Abstract

TCF7L2 variants have been consistently associated with type 2 diabetes (T2D) in populations of different ethnic descent. Among them, the rs7903146 T allele is probably the best proxy to evaluate the effect of this gene on T2D risk in additional ethnic groups. In the present study, we investigated the association between the TCF7L2 rs7903146 polymorphism and T2D in Moroccans (406 normoglycemic individuals and 504 T2D subjects) and in white Austrians (1,075 normoglycemic individuals and 486 T2D subjects). Then, we systematically reviewed the association of this single nucleotide polymorphism (SNP) with T2D risk in a meta-analysis, combining our data with data from previous studies. The allelic odds ratios (ORs) for T2D were 1.56 [1.29–1.89] (p = 2.9 × 10−6) and 1.52 [1.29–1.78] (p = 3.0 × 10−7) in Moroccans and Austrians, respectively. No heterogeneity was found between these two different populations by Woolf test (χ 2 = 0.04, df = 1, p = 0.84). We found 28 original published association studies dealing with the TCF7L2 rs7903146 polymorphism in T2D. A meta-analysis was then performed on 29,195 control subjects and 17,202 cases. No heterogeneity in genotypic distribution was found (Woolf test: χ 2 = 31.5, df = 26, p = 0.21; Higgins statistic: I2 = 14.1%). A Mantel–Haenszel procedure was then performed to provide a pooled odds ratio (OR) of 1.46 [1.42–1.51] (p = 5.4 × 10−140). No publication bias was detected, using the conservative Egger’s regression asymmetry test (t = −1.6, df = 25, p = 0.11). Compared to any other gene variants previously confirmed by meta-analysis, TCF7L2 can be distinguished by its tremendous reproducibility of association with T2D and its OR twice as high. In the near future, large-scale genome-wide association studies will fully extend the genome coverage, potentially delivering other common diabetes-susceptibility genes like TCF7L2.

Copyright information

© Springer-Verlag 2007