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Review
. 2009 Feb 19:10:15.
doi: 10.1186/1471-2350-10-15.

Association between TCF7L2 gene polymorphisms and susceptibility to type 2 diabetes mellitus: a large Human Genome Epidemiology (HuGE) review and meta-analysis

Yu Tong  1 , Ying Lin, Yuan Zhang, Jiyun Yang, Yawei Zhang, Hengchuan Liu, Ben Zhang
Affiliations
Review

Association between TCF7L2 gene polymorphisms and susceptibility to type 2 diabetes mellitus: a large Human Genome Epidemiology (HuGE) review and meta-analysis

Yu Tong et al. BMC Med Genet. .

Abstract

Background: Transcription factor 7-like 2 (TCF7L2) has been shown to be associated with type 2 diabetes mellitus (T2MD) in multiple ethnic groups in the past two years, but, contradictory results were reported for Chinese and Pima Indian populations. The authors then performed a large meta-analysis of 36 studies examining the association of type 2 diabetes mellitus (T2DM) with polymorphisms in the TCF7L2 gene in various ethnicities, containing rs7903146 C-to-T (IVS3C>T), rs7901695 T-to-C (IVS3T>C), a rs12255372 G-to-T (IVS4G>T), and rs11196205 G-to-C (IVS4G>C) polymorphisms and to evaluate the size of gene effect and the possible genetic mode of action.

Methods: Literature-based searching was conducted to collect data and three methods, that is, fixed-effects, random-effects and Bayesian multivariate mete-analysis, were performed to pool the odds ratio (OR). Publication bias and study-between heterogeneity were also examined.

Results: The studies included 35,843 cases of T2DM and 39,123 controls, using mainly primary data. For T2DM and IVS3C>T polymorphism, the Bayesian OR for TT homozygotes and TC heterozygotes versus CC homozygote was 1.968 (95% credible interval (CrI): 1.790, 2.157), 1.406 (95% CrI: 1.341, 1.476), respectively, and the population attributable risk (PAR) for the TT/TC genotypes of this variant is 16.9% for overall. For T2DM and IVS4G>T polymorphism, TT homozygotes and TG heterozygotes versus GG homozygote was 1.885 (95%CrI: 1.698, 2.088), 1.360 (95% CrI: 1.291, 1.433), respectively. Four ORs among these two polymorphisms all yielded significant between-study heterogeneity (P < 0.05) and the main source of heterogeneity was ethnic differences. Data also showed significant associations between T2DM and the other two polymorphisms, but with low heterogeneity (P > 0.10). Pooled ORs fit a codominant, multiplicative genetic model for all the four polymorphisms of TCF7L2 gene, and this model was also confirmed in different ethnic populations when stratification of IVS3C>T and IVS4G>T polymorphisms except for Africans, where a dominant, additive genetic mode is suggested for IVS3C>T polymorphism.

Conclusion: This meta-analysis demonstrates that four variants of TCF7L2 gene are all associated with T2DM, and indicates a multiplicative genetic model for all the four polymorphisms, as well as suggests the TCF7L2 gene involved in near 1/5 of all T2MD. Potential gene-gene and gene-environmental interactions by which common variants in the TCF7L2 gene influence the risk of T2MD need further exploration.

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Figures

Figure 1
Figure 1
Funnel plots of rs7903146 polymorphism studies for T allele vs. C allele (corrected z = 0.82, corrected P = 0.410).
Figure 2
Figure 2
Funnel plots of rs7903146 polymorphism studies for T homozygotes vs. C homozygotes (corrected z = 0.02, corrected P = 0.987).
Figure 3
Figure 3
Funnel plots of rs7903146 polymorphism studies for heterozygotes vs. C homozygotes (corrected z = 0.80, corrected P = 0.426).
Figure 4
Figure 4
Cumulative meta-analysis of the odds ratios of association between rs7903146 polymorphism of TCF7L2 gene and T2DM for T allele vs. C allele.
Figure 5
Figure 5
Cumulative meta-analysis of the odds ratios of association between rs7903146 polymorphism of TCF7L2 gene and T2DM for T homozygotes vs. C homozygotes.
Figure 6
Figure 6
Cumulative meta-analysis of the odds ratios of association between rs7903146 polymorphism of TCF7L2 gene and T2DM for heterozygotes vs. C homozygotes.
Figure 7
Figure 7
Odds ratios of association between rs7903146 polymorphism of TCF7L2 gene and T2DM for T allele vs. C allele.
Figure 8
Figure 8
Odds ratios of association between rs7903146 polymorphism of TCF7L2 gene and T2DM for T homozygotes vs. C homozygotes.
Figure 9
Figure 9
Odds ratios of association between rs7903146 polymorphism of TCF7L2 gene and T2DM for heterozygotes vs. C homozygotes.
Figure 10
Figure 10
Funnel plots of rs12255372 polymorphism studies for T allele vs. G allele (corrected z = 0.96, corrected P = 0.339).
Figure 11
Figure 11
Funnel plots of rs12255372 polymorphism studies for T homozygotes vs. G homozygotes (corrected z = 0.62, corrected P = 0.536).
Figure 12
Figure 12
Funnel plots of rs12255372 polymorphism studies for heterozygotes vs. G homozygotes (corrected z = 0.77, corrected P = 0.442).
Figure 13
Figure 13
Cumulative meta-analysis of the odds ratios of association between rs12255372 polymorphism of TCF7L2 gene and T2DM for T allele vs. H allele.
Figure 14
Figure 14
Cumulative meta-analysis of the odds ratios of association between rs12255372 polymorphism of TCF7L2 gene and T2DM for T homozygotes vs. G homozygotes.
Figure 15
Figure 15
Cumulative meta-analysis of the odds ratios of association between rs12255372 polymorphism of TCF7L2 gene and T2DM for heterozygotes vs. G homozygotes.
Figure 16
Figure 16
Odds ratios of association between rs12255372 polymorphism of TCF7L2 gene and T2DM for T allele vs. H allele.
Figure 17
Figure 17
Odds ratios of association between rs12255372 polymorphism of TCF7L2 gene and T2DM for T homozygotes vs. G homozygotes.
Figure 18
Figure 18
Odds ratios of association between rs12255372 polymorphism of TCF7L2 gene and T2DM for heterozygotes vs. G homozygotes.
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