Influence of rs1292037 Genetic Variant on miR-21 Gene Expression in Patients With Type 1 Diabetes Mellitus: A Case-Control Study.

BACKGROUND AND AIMS: Alterations in the expression pattern of miRNAs seem to be linked with autoimmune diseases such as type 1 diabetes mellitus (T1DM). Regarding the importance of assessing this potential link, we aimed to evaluate the relationship between miR-21 rs1292037 single-nucleotide polymorphism (SNP) and T1DM susceptibility. Furthermore, we investigated the miR-21 expression level in T1DM.

METHODS

A total of 250 T1DM patients and 250 controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and miR-21 expression levels were assessed using real-time PCR. Moreover, the potential targets of miR-21 were investigated using different bioinformatics web servers.

RESULTS

Our results showed that the T/C genotype and the C allele were more frequent in T1DM patients than in controls. Individuals carrying the T/C genotype in overdominant model were 2.74-fold at a higher risk of T1DM (OR = 2.74; 95%CI, 1.78-4.27; p < 0.0001). In addition, miR-21 expression was more than twofold higher in patients than in controls (p < 0.0001) and it was found to be significantly upregulated when carrying the T/C genotype. Regarding miR-21 predicted target genes, its overexpression may be associated with beta cell death, diabetic nephropathy, inflammatory responses, impaired insulin production or secretion, and T-cell cytotoxicity, which are important in the initiation and progression of T1DM.

CONCLUSION

Our results suggested that miR-21 rs1292037 may confer genetic susceptibility to T1DM. Therefore, it seems that this genetic link should be further investigated to enhance diagnostic and therapeutic strategies in these patients.