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

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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.

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Acknowledgments

This work was partly supported by the French Governmental “Agence Nationale de la Recherche”, by the French-Moroccan convention “CNRST-CNRS”, and the charities: “Association Française des Diabétiques” and “Programme national de recherche sur le diabète” and “Association des diabétiques de la Wilaya de Fès”. We thank Marianne Deweider and Frederic Allegaert for the DNA bank management and Stefan Gaget for his help on phenotype databases. We are indebted to all subjects who participated to this study.

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Authors and Affiliations

  1. CNRS, 8090, Institute of Biology, Pasteur Institute, Lille, 59000, France

    Stéphane Cauchi, Hélène Choquet, Christian Dina, David Meyre & Philippe Froguel

  2. Laboratory of Epidemiology, Faculty of Medicine and Pharmacy of Fez, Route Sidi Harazem, B.P 1893, Fez, Morocco

    Younes El Achhab & Chakib Nejjari

  3. Department of Internal Medicine, Krankenhaus Hallein, A-5400, Hallein, Austria

    Franz Krempler

  4. Department of Internal Medicine, Paracelsus Medical University and Landeskliniken Salzburg, A-5020, Salzburg, Austria

    Raimund Weitgasser

  5. Department of Laboratory Medicine, Paracelsus Medical University and Landeskrankenhaus Salzburg, A-5020, Salzburg, Austria

    Wolfgang Patsch

  6. Laboratory of Biochemistry, Faculty of Medicine and Pharmacy of Fez, Route Sidi Harazem, B.P. 1893, Fez, Morocco

    Mohamed Chikri

  7. Section of Genomic Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK

    Philippe Froguel

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  1. Stéphane Cauchi
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  2. Younes El Achhab
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  3. Hélène Choquet
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  4. Christian Dina
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  11. Philippe Froguel
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Correspondence to Philippe Froguel.

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Cauchi, S., El Achhab, Y., Choquet, H. et al. TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis. J Mol Med 85, 777–782 (2007). https://doi.org/10.1007/s00109-007-0203-4

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  • DOI: https://doi.org/10.1007/s00109-007-0203-4

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