Background: Type 2 diabetes mellitus (T2DM) is a metabolic disorder with growing prevalence and increasing economic burden. Based on the role of genetics and epigenetic factors on T2DM, we aimed to carry a systematic review and meta-analysis for all miRNA gene polymorphisms and risk of T2DM. Materials and Methods: A computerized literature search was carried out on PubMed, Web of Science, Scopus, Embase, as well as references of relevant review/meta-analysis. Key search terms were “Diabetes Mellitus, Type 2,” “MicroRNAs,” and “Polymorphism, Single Nucleotide.” All types of observational studies from January 1, 1992, to November 30, 2019, were included, without language restriction. Data analysis was performed using R programming language (3.5.2). Level of heterogeneity was obtained by Cochran's Q test ( P < 0.05), and subgroup analysis was performed based on ethnicity. Results: Thirty-two polymorphisms from fifteen articles were included. Meta-analysis was carried out based on minor allele frequencies. Seven studies with 2193 cases and 3963 controls were included for rs2910164 polymorphism. In subgroup analysis, there were significant results in Caucasian population in dominant model (odds ratio [OR] =1.12; 95% confidence interval [CI]: 0.83–1.51), homozygote model (OR = 1.78; 95% CI: 1.06–3.00), heterozygote model (OR = 1.77; 95% CI: 1.03–3.05), and recessive model (OR = 1.78; 95% CI: 1.07–2.96). Four studies with 2085 cases and 1933 controls were included for rs895819 polymorphism. Overall, there was no significant result for association with rs895819, but subgroup analysis revealed that minor allele significantly decreased the risk of T2DM in Caucasians by recessive model (OR = 0.34; 95% CI: 0.18–0.66), dominant model (OR = 0.70; 95% CI: 0.52–0.94), homozygote model (OR = 0.32; 95% CI: 0.16–0.62), heterozygote model (OR = 0.37; 95% CI: 0.19–0.74), allelic model (OR = 0.67; 95% CI: 0.52–0.85). Conclusion: The minor allele of rs2910164 may increase the risk of T2DM by leading to lower level of miR-146a. In contrast, minor allele of rs895819 may decrease the risk of T2DM by leading to higher level of miR-27a.

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