Micro-RNA 196a2 expression and miR-196a2 (rs11614913) polymorphism in T1DM: a pilot study

Abstract

Background Recent emerging evidence supports the role of miR-196a2 in various human diseases. However, its role in type 1 diabetes mellitus (T1DM) is still underestimated. We aimed, for the first time, to investigate the expression of miR-196a2 in T1DM and the association of miR-196a2 (rs11614913) polymorphism with susceptibility of T1DM in a sample of patients from Cairo, Egypt. Methods The study included 150 patients and 150 healthy subjects. Evaluation of rs11614913 genotypes and miR-196a2 expression was done using the allelic discrimination and quantitative reverse transcriptase polymerase chain reaction (PCR) method, respectively. Results The Hardy-Weinberg equilibrium of single nucleotide polymorphism(SNP) was detected among controls (p = 0.2). Our results revealed that the TT genotype was more frequent in patients (22.6%) than controls (10%) while the CC genotype was more frequent in controls (47.3%) than patients (39.3%) (p = 0.01). The frequency of the T allele was significantly higher in patients than in controls (41.7 vs. 31.3%), while the C allele was more frequent in controls (p = 0.008). After adjustment for traditional risk factors, the association of the TT genotype with T1DM remained significant (TT vs. CC, odds ration [OR] = 3.2, 95% confidence interval [CI]: 1.4–7.4, p = 0.005). Power analysis of the data yielded a statistical power of 80% for the miR-196a2 rs11614913 with T1DM. Relative expression of miR-196a2 showed significant decrease in patients compared to controls (median = 0.09, 0.5, interquartile range [IQR] = 0.03–1.6, 0.1–2.1). However, miR-196a2 expression showed no significant difference between different rs11614913 genotypes (p = 0.5). Conclusions Our findings demonstrated that miR-196a rs11614913 is associated with T1DM and decreased expression of miR-196a2 may play a role in pathogenesis of T1DM.

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 ]. In the current study, we found that the genotype TT (n = 76/22.4%) of rs11614913 T/C was more frequent in cases as compared to controls (n = 33/13.98%).…”

“…The study stated that the association of the TT genotype with T1DM remained significant. The study also reported decreased relative expression of miR-196a2 in patients compared to controls [ 44 ]. In contrast to our studies, some researchers have reported a higher frequency of T alleles in patients than controls and the T allele has been reported to decrease the risk of T2DM.…”

Genetic Variants in miRNAs Are Associated With Risk of Non-syndromic Tooth Agenesis

“…miR-146a/rs2910164 was associated with the non-syndromic orofacial cleft (Pan et al, 2018) and bladder cancer (Wang et al, 2012). miR-196a2/rs11614913 showed an association with the hepatocellular carcinoma (Zheng et al, 2017) and type 1 diabetes mellitus (Ibrahim et al, 2019).…”

Influence of rs1292037 Genetic Variant on miR-21 Gene Expression in Patients with type 1 Diabetes Mellitus

“…Multiple studies have investigated the role of miRNAs-relates SNPs in the incidence and prognosis of T1DM. For instance, miR-196a rs11614913 is reported to be associated with the pathogenesis of T1DM (13).…”

“…Studies have vastly reported that SNPs in the miRNAs coding genes can affect the binding a nity and binding ability of the miRNAs and even can alter the target mRNA (12). miRNAs-related SNPs are known to be associated with the incidence of several diseases including T1DM (13). Limited studies have investigated the association between miR-21 rs1292037 SNP and human-related diseases to this date.…”