Evaluation of Discoidin Domain Receptor- 1 and Ceruloplasmin as Early Diagnostic Markers in Type 2 Diabetic Patients with Nephropathy

Abstract

Diabetic nephropathy is considered a major microvascular complication of diabetes. This study aims to evaluate serum levels of Discoidin domain receptor-1 (DDR1) and Ceruloplasmin (CP) as early diagnostic markers in type 2 diabetes patients with nephropathy. In addition to evaluating the association between single nucleotide polymorphisms (SNPs) in genes encoding these proteins, CP and DDR1.

Subjects and Methods: This studyincluded15 healthy subjects as controls (group 1) and 58 patients with type two diabetic nephropathy classified according to albumin/creatinine ratio (ACR). Group 2, which includes 17 patients with “normoalbuminuria (UACR<30 mg/g)”. Group 3, which includes 21 patients with microalbuminuria (UACR= 30-300 mg/g), group 4 which includes 20 patients with macroalbuminuria (UACR>300mg/g). In the studied groups, we measured these parameters: fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c), urea, Creatinine, lipid profile, Glomerular filtration rate (GFR), c-peptide, ceruloplasmin, and Discodin domain receptor -1 in addition to a determination of genotype frequencies for CP (rs11708215) and DDR-1 (rs4618569) genes polymorphisms using Real-time polymerase chain reaction (RT-PCR). 

ResultsIn this study:we found that ceruloplasmin and DDR-1 were significantly elevated (p<0.001) in micro-and macroalbuminuric diabetic groups in comparison to the control group and diabetic normoalbuminuric groups. We found that DDR-1 was correlated positively with LDL and negatively correlated with BMI. Also found a significantly elevated DDR-1 AG genotype in diabetic nephropathy groups as compared to the control group with p=0.034. Also statistically insignificant, it appears that the AG genotype of CP (rs11708215).With a p=0.67, indicated a greater incidence of the illness compared to the control group.

Conclusions: DDR-1 is more specific and more sensitive than Ceruloplasmin. So DDR-1 marker may serve as an early diagnostic marker in type 2 diabetic patients with nephropathy. Also, for the DDR-1 gene variant (rs4618569), the AG genotype showed a high statistical significance of the disease compared to the control group. However, the CP-gene variant (rs11708215) was not significantly associated with DN.