Cauchi Stéphane, El Achhab Younes, Choquet Hélène, Dina Christian, Krempler Franz, Weitgasser Raimund, Nejjari Chakib, Patsch Wolfgang, Chikri Mohamed, Meyre David, Froguel Philippe
CNRS, 8090, Institute of Biology, Pasteur Institute, Lille, 59000, France.
J Mol Med (Berl). 2007 Jul;85(7):777-82. doi: 10.1007/s00109-007-0203-4. Epub 2007 May 3.
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.
在不同种族血统的人群中，TCF7L2基因变异一直与2型糖尿病（T2D）相关。其中，rs7903146的T等位基因可能是评估该基因对其他种族T2D风险影响的最佳指标。在本研究中，我们调查了摩洛哥人（406名血糖正常个体和504名T2D患者）以及奥地利白人（1075名血糖正常个体和486名T2D患者）中TCF7L2 rs7903146多态性与T2D之间的关联。然后，我们在一项荟萃分析中系统回顾了该单核苷酸多态性（SNP）与T2D风险的关联，将我们的数据与先前研究的数据相结合。摩洛哥人和奥地利人中T2D的等位基因优势比（OR）分别为1.56 [1.29 - 1.89]（p = 2.9 x 10(-6)）和1.52 [1.29 - 1.78]（p = 3.0 x 10(-7)）。通过Woolf检验发现这两个不同人群之间不存在异质性（chi (2) = 0.04，df = 1，p = 0.84）。我们发现有28项原始发表的关于T2D中TCF7L2 rs7903146多态性的关联研究。然后对29,195名对照受试者和17,202例病例进行了荟萃分析。未发现基因型分布存在异质性（Woolf检验：chi (2) = 31.5，df = 26，p = 0.21；Higgins统计量：I2 = 14.1%）。然后采用Mantel - Haenszel方法得出合并优势比（OR）为1.46 [1.42 - 1.51]（p = 5.4 x 10(-140)）。使用保守的Egger回归不对称检验未检测到发表偏倚（t = -1.6，df = 25，p = 0.11）。与先前通过荟萃分析确认的任何其他基因变异相比，TCF7L2因其与T2D关联的高度可重复性以及其OR值高出两倍而脱颖而出。在不久的将来，大规模全基因组关联研究将全面扩展基因组覆盖范围，有可能发现其他像TCF7L2这样常见的糖尿病易感基因。
