New risk factors in diabetic nephropathy: microRNA-196-3p and microRNA-203.

BACKGROUND

The aim of this study was to evaluate changes in the serum levels of miR-98, miR-184, miR-185, miR-203 and miR-196a-3p in type 2 diabetes mellitus (T2DM) patients with diabetic nephropathy (DN) and to associate the changes in microRNA levels with urinary albumin excretion (UAE).

METHODS

The study included 35 healthy individuals aged between 18-65 years, 40 T2DM patients with normoalbuminuria, 40 T2DM patients with microalbuminuria, and 35 T2DM patients with macroalbuminuria. Metabolic laboratory parameters, microalbumin levels in 24-hour urine samples were measured in all groups. Serum levels of vascular endothelial growth factor-A (VEGF-A) and transforming growth factor-β (TGF-β) were measured quantitatively by Enzyme-Linked Immunosorbent Assay (ELISA). Circulating miRNA levels were determined by real-time quantitative PCR.

RESULTS

Serum miR-196a-3p levels were reduced in the normoalbuminuria group compared to the healthy control group. In the macroalbuminuria and microalbuminuria groups, miR-196a-3p levels were higher compared to the normoalbuminuria group. In addition, increase in miR-196a-3p levels in the macroalbuminuria group was more prominent than the microalbuminuria group. Serum miR-203 levels were significantly higher in the macroalbuminuria group compared to healthy controls, microalbuminuria and normoalbuminuria groups; these levels were also higher in the microalbuminuria group compared to normoalbuminuria group. In logistic regression analysis, serum miR-196a-3p and miRNA-203 levels were independently correlated to UAE.

CONCLUSIONS

Increased serum levels of miR-203 and miR-196a-3p are independent risk factors of UAE which is a marker of DN.