MicroRNA-499a (rs3746444A/G) gene variant and susceptibility to type 2 diabetes-associated end-stage renal disease.

ABSTRACT

Diabetic nephropathy (DN) is a major risk factor for end-stage renal disease (ESRD). MicroRNAs (miRNAs/miRs) and their variants may be implicated in health and disease, including DN. The present study aimed to investigate the association of the miRNA-499a gene (MIR499A) A/G seed region variant (rs3746444) with DN-associated ESRD susceptibility in patients with diabetes mellitus, and to determine whether there was an association between the different genotypes and the patients' laboratory and clinical data. A case-control pilot study was conducted on 180 adult patients with type 2 diabetes mellitus. A total of 90 patients with ESRD on regular hemodialysis were considered as the cases, and 90 age-, sex- and ethnicity-matched diabetic patients with normo-albuminuria were considered as the controls. MIR499A genotyping was performed using a TaqMan Real-Time allele discrimination assay. Results demonstrated that the MIR499A rs3746444*G variant conferred susceptibility to the development of ESRD under co-dominant [(odds ratio (95% confidence interval) 2.49 (1.41-3.89) and 2.41 (1.61-6.68) for heterozygous and homozygous comparison, respectively], dominant [2.30 (1.18-3.90)] and allelic [1.82 (1.17-2.83)] models. Different genotypes of the specified variant did not exhibit significant associations with the clinic-laboratory data of the studied patients or the circulating miR-499a plasma levels. In conclusion, results of the present study suggested that MIR499A rs3746444 may be a susceptibility variant for DN-associated ESRD in the study population. However, larger sample size studies with different ethnicities are warranted to verify these findings.