VEGF -460 genotype plays an important role in progression to chronic kidney disease stage 5

Background. Changes in renal vasculature, with vascular and interstitial fibrosis, are hallmarks of progression to chronic kidney disease (CKD) stage 5. Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor. Transforming growth factor-β1 (TGF-β1) plays a critical role in promoting extracellular matrix (ECM) deposition and fibrosis. This study investigates whether genetic polymorphisms of VEGF or TGF-β1 are associated with (i) progressive decline in renal function in patients with glomerular disorders (cohort 1) and (ii) predisposition to CKD stage 5 in a separate group of renal transplant recipients with various primary diseases (cohort 2). Methods. Two patient groups were studied. Cohort 1 comprised 91 patients with biopsy-proven glomerular disease who were followed-up for 5 years before categorization as either non-progressors (with stable serum creatinine or ≤30% increase over 5 years, n= 39) or progressors (requiring dialysis, transplantation or whose serum creatinine increased by >30% over 5 years, n= 52). Cohort 2 comprised 107 patients with various primary renal diseases, who had reached CKD stage 5 and undergone renal transplantation at the time of study. All patients were genotyped for the VEGF polymorphisms at positions -460 (C/T) and +405 (G/C). Linkage disequilibrium (LD) was established using EHplus. SNPHAP was used to estimate haplotype frequency and to infer haplotypes to all patients. Cohort 1 patients were genotyped for the TGF-β1 polymorphisms at positions -800, -509, codons 10 and 25. Genotyping was performed by polymerase chain reaction-restriction length polymorphism (PCR-RFLP). Results. In cohort 1, there was a significant increase in frequency of the -460 VEGF CC genotype 30.8 vs 5.1%, P=0.008; odds ratio (OR), CC vs TT 10.67, 95% confidence interval (CI), 1.94-58.72 and C allele 56.7 vs 37.2%, P=0.009; OR 2.22, 95% CI, 1.21-4.04, in the progressor patients when compared with the non-progressors. In cohort 2, there was a significant increase in the VEGF -460 CC genotype when compared with healthy volunteers 37 vs 20.8%, P=0.011; OR CC vs TT 1.59, 95% CI, 0.72-3.51. The -460 and +405 polymorphisms were in LD P