Association of microRNA gene polymorphisms with Type 2 diabetes mellitus: A systematic review and meta-analysis

Abstract

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.

Relationship of microRNA locus with type 2 diabetes mellitus: a case–control study

“…In our study, a Bonferroni correction was harnessed to confirm our findings. After adjustment, the correlation of rs2910164 with the occurrence of T2DM also existed in overall comparison and in BMI ≥24 kg/m 2 and never drinking subgroups, which was similar to the findings of a more recent meta-analysis [30] . In the future, more well-matched investigations are needed to confirm or refute our observations.…”

“…To determine the potential relationship between miR-SNPs and T2DM, we selected the miR-146a rs2910164 C>G, miR-196a2 rs11614913 T>C and miR-499 rs3746444 A>G loci polymorphism according to the literature, which was significantly associated with cancer ( 20 , 21 , 22 , 23 ), coronary artery disease ( 35 , 36 ) and type 2 diabetes ( 25 , 26 , 27 , 28 , 30 ), in some studies.…”

“…The included participants were more limited, and the findings were more conflicting. In 2020, Gholami et al systematically reviewed the SNPs associated with T2DM ( 30 ). In view of the potential effect of miR-SNPs in the occurrence of T2DM, we selected rs11614913, rs2910164 and rs3746444 loci and carried out an investigation to identify whether these miR-SNPs could influence the risk of T2DM.…”

Deciphering the Variants Located in the MIR196A2, MIR146A, and MIR423 with Type-2 Diabetes Mellitus in Pakistani Population

“…A previous study has shown that miR-196a rs11614913 T/C is linked with T2DM [ 29 ]. Downregulation of its mature miRNA may play a pivotal role in T1DM [ 44 ].…”

“…It is already known that SNP rs11614913 is in MIR196A and is located in chromosome 17 between HOX genes. It also interacts with HOX genes [ 28 , 29 ]. The previous study has shown that HOX genes play a pivotal role in the initiation of fetal organs, including the pancreas.…”