Abstract
PURPOSE: Diabetic nephropathy (DN) is the main cause of end-stage renal disease. The renin-angiotensin system and inflammatory pathways are suggested to contribute to renal injuries in diabetes. Endoplasmic reticulum aminopeptidase 1 (ERAP1) breaks Ang II into less harmful derivatives. This study aimed to investigate the expression level of ERAP1 and TLR4 genes in association with serum Ang II in DN patients. METHODS: In 80 type 2 diabetic (T2DM) patients with nephropathy, 80 T2DM patients without nephropathy, and 60 healthy controls, polymorphisms of the ERAP1 gene (rs28096, rs34750, rs26653, rs3734016, and rs30187), as well as ERAP1 and TLR4 gene expression were evaluated with RT-PCR. Serum Ang II level was quantified using ELISA. RESULTS: Serum Ang II levels were significantly higher in DN patients compared to T2DM patients without nephropathy and healthy controls (P-values: 0.012 and 0.006, respectively). ERAP1 expression was also enhanced in the DN group compared to T2DM and healthy individuals (P-value: 0.033 and 0.017, respectively), and showed a significant association with Ang II levels [R: 0.43, R2: 0.184 (p-value = 0.02)]. In both patient groups, TLR4 expression was increased compared to healthy controls (P-value: 0.003 and 0.004). ERAP1 rs30187 TT was more frequent in the DN group (P-value 0.021). CONCLUSION: Increased levels of Ang II and enhanced expression of ERAP1 might be prognostic of developing nephropathy in T2DM patients.