Diagnostic efficacy of cystatin-c in association with different ACE genes predicting renal insufficiency in T2DM

Abstract

Abstract Diabetic nephropathy (DN) seems to be the major cause of chronic kidney disease that may finally lead to End Stage Renal Disease. So, renal function assessment in type 2 diabetes mellitus (T2DM) individuals is very important. Clearly, DN pathogenesis is multifactorial and different proteins, genes and environmental factors can contribute to the onset of the disease. We assessed sensitive and specific biomarkers (in blood and urine) which can predict kidney disease susceptibility among T2DM patients. Serum cystatin-c (cyst-c) in blood and urinary hemeoxygenase (HO-1) in addition to ACE I/D polymorphism and ACE G2350A genotypes. Hundred and eight T2DM patients and 85 controls were enrolled. Serum cystatin-c and urinary (HO-1) were tested by ELISA. Genetic determination of both ACE I/D polymorphism and ACE G2350A genotypes was performed by PCR for all participants. Significant rise in serum cystatin-c and urinary HO-1 levels were shown in diabetic groups compared with control group. Moreover, GG genotype of ACE G2350A gene in diabetic group was associated with rise in serum cystatin-c and urinary HO-1 compared with control group. Mutant AA genotype demonstrated increase in urinary HO-1. DD polymorphism was associated with rise in serum creatinine and cyst-c in diabetic group. Positive correlation was seen between duration of diabetes and serum cyst-c and between serum glucose and urinary (HO-1) in diabetic group. The results from this study indicated an association of serum cystatin-c with GG genotype of ACE G2350A in conjugation with DD polymorphism of ACE I/D which could be an early predictor of tubular injury in T2DM diabetic patients.