الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Diabetic nephropathy (DN) is one of the most common diabetic microvascular disorders. It is a primary source of morbidity and mortality, and it mostly leads to kidney failure. With the continuous rise in the frequency of diabetes over the last few years, the prevalence of DN has also raised significantly. Current tests’ accuracy in predicting the beginning, development, and response to various diabetic nephropathy therapies is still unclear, leading to a search for new sensitive and specific biomarkers.
In this study we aimed to evaluate serum levels of Discoidin domain receptor-1 (DDR1) and Ceruloplasmin (CP) as early diagnostic markers in type 2 diabetic patients with nephropathy. In addition, the association between single nucleotide polymorphisms (SNPs) in genes encoding these proteins, CP and DDR1 were determined.
This study included 15 healthy subjects as controls (group 1) and 58 patients with type 2 diabetic patients with nephropathy who were classified into 17 type 2 diabetic patients with normoalbuminuria (UACR<30 mg/g) as group 2, 21 diabetic patients with microalbuminuria (UACR= 30-300 mg/g) as group 3 and
20 diabetic patients with macroalbuminuria (UACR > 300mg/g) as group 4.
This classification was according to albumin/Creatinine ratio (ACR). In the studied groups, we measured these parameters: fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c), urea, creatinine, lipid profile, glomerular filtration rate (GFR), Ceruloplasmin, and Discoidin domainreceptor-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).
There were significantly higher levels of DDR-1 in the normo and microalbuminuric diabetic groups than in the control group (n=73, median 4443.65 pg. /ml (interquartile range 3590.53-8056.05), but there were no significant differences between the control and macroalbuminuric diabetic groups (p=0.06). In addition, compared to the control group, CP was significantly higher (p<0.05) in the micro-and normoalbuminuric diabetic groups (median 440 pg. /ml; interquartile range: 75.00-832.50) .In group 2, DDR-1 was positively correlated with LDL and CP and negatively correlated with BMI. Also, DDR-1 was significantly correlated with Cp in group 3, whereas DDR-1 was positively correlated with Systolic blood pressure (SBP) and CP in group 4 and Cp was positively correlated with Systolic and Diastolic blood pressure.
DDR-1 is more specific than CP in normo and microalbuminuric diabetic groups, but it cannot be used as a diagnostic marker for type 2 DN. Cp 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.