Abstract
Type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) seriously impact the prognosis and survival of patients. Abundant studies suggest that single nucleotide polymorphisms (SNPs) within regulatory regions of miRNAs modulate progression of various diseases including DM and DN. However, evidence for exploring the mechanism in DM and DN are still insufficient. This study was performed to discuss the association of SNPs in the regulatory region of hsa-miR-34a with DM or DN susceptibility in the southwest Chinese Han population. Three SNPs (rs12128240, rs2666433, rs6577555) in miR-34a were analyzed in the T2DM patients with or without DN and normal controls. RT-qPCR was performed to measure expression of miR-34a. Real-time PCR was used for amplification of SNPs. MiR-34a was over-expressed in T2DM and DM patients. Both the distribution of GG genotypes and the G allele frequency of rs2666433 were significantly different between the T2DM and control groups (P=0.009, P=0.008 respectively). Univariate analysis with additive and recessive models for rs2666433 polymorphisms showed an association with DM (P=0.023; P=0.009 respectively), and a stronger association was found in an additive model (P=0.001) when compared with DN. After adjustment for clinical covariates, the GG genotype was still significantly different for the recessive model (OR 2.297; CI 1.031-5.121; P=0.042) in T2DM by multivariate analysis. In conclusion, our study demonstrates that a potential variant rs2666433 in the miR-34a regulatory region may significantly associate with the occurrence of T2DM.