Altered expression of WFS1 and NOTCH2 genes associated with diabetic nephropathy in T2DM patients

The increased incidence of type 2 diabetes mellitus (T2DM) and the importance of early identification and management of its complications, especially diabetic nephropathy (DN), have spotted the light on genetic factors that increase risk of T2DM and its related nephropathy. The present study aimed at investigating expression of (KCNJ11, ABCC8, JAZF1, WFS1, PPARG, NOTCH2 and EXOSC4) genes in peripheral blood of T2DM patients.

The study included 30 non-complicated T2DM patients, 30 patients with DN and 40 healthy controls. Quantitative Real Time PCR Array was used to study gene expression.

NOTCH2 showed higher expression while KCNJ11, JAZF1, WFS1 and PPARG genes showed lower expression in DN patients compared to non-complicated patients. KCNJ11, JAZF1, WFS1, PPARG, and EXOSC4 expression showed significant negative correlation with microalbumin, while NOTCH2 expression was significantly positively correlated with microalbumin. AS regard HbA1c and studied genes expression, there was significant negative correlation between WFS1 expression and HbA1c, while NOTCH2, KCNJ11, JAZF1, PPARG, EXOSC4 expression didn't show significant correlation with HbA1c. Risk ratio of studied genes expression showed that WFS1 and NOTCH2 had highest risk ratio (30) and highest sensitivity and specificity, in relation to DN and they were the best predictors in the group of studied genes at cut off value of ≤0.861 for WFS1 and ≥0.678 for NOTCH2.

Altered expression of WFS1 and NOTCH2 genes may play a role in pathogenesis and development of DN in patients with T2DM. These results may contribute in early identification and management of DN.