Association between TCF7L2 gene polymorphisms and susceptibility to Type 2 Diabetes Mellitus: a large Human Genome Epidemiology (HuGE) review and meta-analysis

被引:188
作者
Tong, Yu [3 ]
Lin, Ying [1 ,2 ]
Zhang, Yuan [4 ]
Yang, Jiyun [1 ,2 ]
Zhang, Yawei [5 ]
Liu, Hengchuan [6 ]
Zhang, Ben [1 ,2 ,7 ]
机构
[1] Sichuan Acad Med Sci, Sichuan Prov Key Lab Human Dis Gene, Chengdu 610072, Peoples R China
[2] Sichuan Prov Peoples Hosp, Chengdu 610072, Peoples R China
[3] Sichuan Univ, W China Univ Hosp 2, Open Lab, Chengdu 610041, Peoples R China
[4] Hlth Bur Wuhou Dist, Dept Community Hlth, Chengdu 610041, Peoples R China
[5] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA
[6] Sichuan Univ, W China Sch Publ Hlth, Dept Lab Med, Chengdu 610041, Peoples R China
[7] Sichuan Acad Med Sci, Dept Lab Med, Chengdu 610072, Peoples R China
关键词
IMPAIRED GLUCOSE-TOLERANCE; ENZYME IDE GENE; WIDE ASSOCIATION; BETA-CATENIN; INCREASING PREVALENCE; URBAN-POPULATION; FASTING GLUCOSE; INCREASED RISK; ETHNIC-GROUPS; VARIANTS;
D O I
10.1186/1471-2350-10-15
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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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页数:25
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