MicroRNA genetic variations: association with type 2 diabetes

Abstract

MicroRNAs are small single-stranded molecules that have emerged as important genomic regulators in different pathways. Different studies have shown that they are implicated in the metabolism and glucose homeostasis, and therefore, they could also be involved in the pathogenesis of metabolic disorders such as type 2 diabetes (T2DM). The aim of this study was to verify whether genetic variations in candidate microRNA (miRNA or miR) genes could contribute to T2DM susceptibility. We have selected 13 miRNAs as candidate loci according to literature data and to a computational analysis. MicroRNA genes were analyzed by direct sequencing in a cohort of 163 Italian T2DM patients and 185 healthy controls. We identified 6 novel variants never described before and 9 SNPs already described in databases. Five newly identified variants were found only in the cases group. We performed a case/control association study to test the associations of particular alleles/genotypes of identified SNPs with the disease. Two polymorphisms were associated with T2DM susceptibility: in particular, the G allele of rs895819 in hsa-mir-27a has shown a significantly protective effect (OR = 0.58 and P = 0.008), while the G allele of rs531564 in hsa-mir-124a appears to be a risk allele (OR = 2.15, P = 0.008). This is the first report indicating that genetic polymorphisms in miRNA regions could contribute to T2DM susceptibility.

Association study of the miRNA-binding site polymorphisms of CDKN2A/B genes with gestational diabetes mellitus susceptibility

“…Emerging evidence shows that single nucleotide polymorphisms (SNPs) within miRNA genes or miRNA-binding sites can alter the binding affinity of miRNAs to target mRNAs and thus influence target gene expression [7]. These kinds of SNPs are known to contribute to susceptibility to a variety of diseases, including cancer, cardiovascular disease, osteoporosis, and T2DM [8][9][10][11]. However, no studies to date have attempted to identify SNPs in miRNA-binding sites (miR-bindingSNPs) that associate with GDM risk.…”

Mir-338-3p Mediates Tnf-A-Induced Hepatic Insulin Resistance by Targeting PP4r1 to Regulate PP4 Expression

“…miRNAs are associated with different biological processes, including cell proliferation, differentiation and apoptosis [12]. It has been reported that aberrant miRNA expression is associated with the pathogenesis of type 2 diabetes [13, 14]. For example, miR-375 could regulate insulin secretion [15].…”

The pre-mir-27a variant rs895819 may contribute to type 2 diabetes mellitus susceptibility in an Iranian cohort

“…Moreover, we found that genotype distributions were significantly different between groups (p < 0.05) and that the rs895819-C allele is more frequent in controls (p = 0.030, OR = 0.72, 95 % CI 0.53-0.97). association studies (GWAS) recently suggested that also genetic variations in noncoding regions could give a contribution to the disease phenotype [1,4]. MicroRNAs (miRNAs), a new family of small noncoding RNAs, have demonstrated to play substantial roles in many pathophysiological processes [5].…”