Expression of microRNA-377 and microRNA-192 and their potential as blood-based biomarkers for early detection of type 2 diabetic nephropathy

The increased incidence of diabetic nephropathy (DN) in type 2 diabetes (T2D) requires novel markers for the early detection of DN. Previously, microRNAs (miRs) have been demonstrated to be promising disease biomarkers. The present study evaluated the biomarker potential of DN-associated miR-377 and miR-192 in the early stages of DN. The study included 85 participants: 55 patients with T2D (30 without DN and 25 with DN) and 30 healthy controls. The patients with T2D were classified according to albumin-to-creatininc ratio and were split into three groups: Normoalbuminuric group (n=30), microalbuminuric group (n=15) and macroalbuminuric group (n=10). Reverse transcription-quantitative polymerase chain reaction analysis was used to evaluate blood miR expression. It was observed that there was higher miR-377 expression and lower miR-192 expression in T2D patients with and without DN compared with healthy controls (P<0.05). miR-377 was higher in the normoalbuminuric group and gradually increased in the microalbuminuric and macroalbuminuric groups (P<0.05), whereas miR-192 was lower in the macroalbuminuric group compared with the normoalbuminuric group (P<0.05). Regression analysis revealed direct associations between the two miRs and albuminuria (P<0.05). miR-377 was independently associated with DN risk, even following multivariable adjustment, and albuminuria was the only predictor of miR-377 (P<0.001). In discriminating overall patients from healthy subjects, ROC analysis revealed areas under the curve (AUCs) of 0.851 for miR377 and 0.774 for miR-192 (P<0.001). In discriminating the normoalbuminuric group from the microalbuminuric/macroalbuminuric groups, the AUCs were 0.711 (P=0.008) and 0.70 (P=0.049) for miR-377 and miR-192, respectively. In patients with microalbuminuria and macroalbuminuria, miR-377 correlated positively with albuminuria and negatively with renal function, whereas miR-192 correlated negatively with albuminuria and positively with renal function (P=0.001), and the two miRs were correlated with known risk factors of DN (P<0.05). The results suggested that blood-based miR-377 and miR-192 may serve as potential biomarkers for early detection of DN. Further validation studies are required with larger sample sizes.