title: TCF7L2 is reproducibly associated with type 2 diabetes in various ethnic groups: a global meta-analysis.
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 x 10(-6)) and 1.52 [1.29-1.78] (p = 3.0 x 10(-7)) in Moroccans and Austrians, respectively. No heterogeneity was found between these two different populations by Woolf test (chi (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: chi (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 x 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.
authors.affiliation: CNRS, 8090, Institute of Biology, Pasteur Institute, Lille, 59000, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Cauchi
authors.forename: Younes
authors.initials: Y
authors.lastname: El Achhab
authors.forename: Hélène
authors.initials: H
authors.lastname: Choquet
authors.forename: Christian
authors.initials: C
authors.lastname: Dina
authors.forename: Franz
authors.initials: F
authors.lastname: Krempler
authors.forename: Raimund
authors.initials: R
authors.lastname: Weitgasser
authors.forename: Chakib
authors.initials: C
authors.lastname: Nejjari
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Patsch
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chikri
authors.forename: David
authors.initials: D
authors.lastname: Meyre
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
chemical_list: D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein