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Association between polymorphisms in microRNAs and susceptibility to diabetes mellitus: A meta-analysis.

ABSTRACT: BACKGROUND:Accumulated evidence has indicated the associations between single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) and the susceptibility to diabetes mellitus (DM), but the conclusions remain controversial. This study was to investigate the true contribution of miRNA SNPs to the risk of DM by using a meta-analysis of all the published studies. METHODS:Relevant studies were identified in the databases of PubMed and the Cochrane Library databases. The strength of associations between miRNA polymorphisms and DM risk was assessed by odds ratios (ORs) and 95% confidence intervals (95% CIs) under five genetic models using the STATA software. RESULTS:Six studies, containing 2773 cases and 2632 controls, were enrolled, 5 of which evaluated miR-146a (rs2910164), 4 for miR-27a (rs895819), and 3 for miR-124 (rs531564) and 2 for miR-375 (rs6715345), miR-128a (rs11888095), miR-194a (rs3820455). The meta-analysis indicated that the G allele or GG genotype of miR-146a rs2910164 was associated with a significantly increased risk for DM compared with C allele or GC/CC genotype in Latin American population; CC genotype of miR-27a rs895819 polymorphism was associated with a significantly decreased risk for DM in Asian population compared with the TT genotype; patients carrying with CC genotype of miR-124 rs531564 had a lower probability to develop DM regardless of ethnicity; no associations were identified between polymorphisms in miR-375, miR-128a, miR-194a and the susceptibility to DM. CONCLUSION:Our study suggests that miR-146a/miR-27a and miR-124 polymorphisms may be ethnicity-dependent or -independent susceptibility factors to DM, respectively.

SUBMITTER: Chen X

PROVIDER: S-EPMC6946283 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Association between polymorphisms in microRNAs and susceptibility to diabetes mellitus: A meta-analysis.

Chen Xi X Wang Wenjing W Li Ruien R Yu Jing J Gao Lei L

Medicine 20191101 44

<h4>Background</h4>Accumulated evidence has indicated the associations between single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) and the susceptibility to diabetes mellitus (DM), but the conclusions remain controversial. This study was to investigate the true contribution of miRNA SNPs to the risk of DM by using a meta-analysis of all the published studies.<h4>Methods</h4>Relevant studies were identified in the databases of PubMed and the Cochrane Library databases. The strength of as ...[more]

PMID: 31689753

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Project description: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.

Project description:Background: Insulin-like growth factor-1 (IGF-1) has been demonstrated to increase fatty acid β oxidation during fasting, and play an important role in regulating lipid metabolism and type 2 diabetes mellitus (T2DM). The rs35767 (T > C) polymorphism, a functional SNP was found in IGF-1 promoter, which may directly affect IGF-1 expression. However, the inconsistent findings showed on the IGF-1 rs35767 polymorphism and T2DM risk. Methods: We performed a comprehensive meta-analysis to estimate the association between the IGF-1 rs35767 and T2DM risk among four genetic models (the allele, additive, recessive and dominant models). Results: A total 49,587 T2DM cases and 97,906 NDM controls were included in the allele model, a total 2256 T2DM cases and 2228 NDM controls were included in the other three genetic models (the additive; recessive and dominant models). In overall analysis, the IGF-1 rs35767 was shown to be significantly associated with increased T2DM risk for the allele model (T vs. C: OR = 1.251, 95% CI: 1.082-1.447, p = 0.002), additive model (homozygote comparisons: TT vs. CC: OR = 2.433, 95% CI: 1.095-5.405, p = 0.029; heterozygote comparisons: TC vs. CC: OR = 1.623, 95% CI: 1.055-2.495, p = 0.027) and dominant model (TT + CT vs. CC: OR = 1.934, 95% CI: 1.148-3.257, p = 0.013) with random effects model. After omitting Gouda's study could reduce the heterogeneity, especially in the recessive model (TT vs. CC + CT: I2 = 38.7%, p = 0.163), the fixed effects model for recessive effect of the T allele (TT vs. CC + CT) produce results that were of borderline statistical significance (OR = 1.206, 95% CI: 1.004-1.448, p = 0.045). And increasing the risk of T2DM in Uyghur population of subgroup for the allele model. Conclusion: The initial analyses that included all studies showed statistically significant associations between the rs35767 SNP and type 2 diabetes, but after removing the Gouda et al. study produced results that were mostly not statistically significant. Therefore, there is not enough evidence from the results of the meta-analysis to indicate that the rs35767 SNP has a statistically significant association with type 2 diabetes.

Dataset Information

Association between polymorphisms in microRNAs and susceptibility to diabetes mellitus: A meta-analysis.

Publications

Association between polymorphisms in microRNAs and susceptibility to diabetes mellitus: A meta-analysis.

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