Introduction: Vascular endothelial growth factor (VEGF) regulates vasculogenesis in physiological and pathological states. We evaluated the role of VEGF single-nucleotide polymorphisms (SNPs) -1154 G/A, -2578 C/A, +936 C/T, and -2549 Ins/Del in chronic allograft nephropathy.
Methods: Blood samples were collected before renal transplantation, and DNA was extracted. Genotyping of VEGF SNPs -1154 G/A (rs1570360), -2578 C/A (rs699947), +936 C/T (rs112005313), and -2549 Ins/Del (18bpindel) polymorphisms were carried out. Relative quantification of VEGF-A mRNA expression for 4 VEGF SNPs were quantified by the 2-ΔΔCt algorithm. Kidney allografts were categorized into graft loss (n = 98) and normally functioning (n = 174) groups. Genotype frequencies were calculated using additive, dominant, and recessive models. Hardy-Weinberg Equilibrium was assessed between outcome groups by standard procedure using χ2 analysis. The cumulative allograft survival was estimated by Kaplan-Meier analysis and compared among VEGF genotypes by the log-rank test. Study limitations were the lack of VEGF serum levels, donor-specific antigens, and protocol biopsies.
Results: There was an association of AA (hazard ratio = 2.42, P = 0.0001) and CA (hazard ratio = 1.83, P = 0.009) genotypes of -2578 C/A SNP with graft loss. After adjustment for transplant-related covariates, associations of VEGF SNPs -2578 C/A and -2549 Ins/Del with graft failure were found to be significant. There was prolonged graft survival for cases with the CC genotype of VEGF -2578 C/A SNP. The carrier -2578*CC, -1154*GG, and +936*CC genotypes were shown to have a strongly protective association. There was no association with posttransplantation lymphomas.
Conclusion: Recipients of kidney allografts possessing low-producing VEGF genotypes are associated with less prolonged graft survival.
Keywords: VEGF −2578 C/A; chronic allograft dysfunction; single-nucleotide polymorphism; vascular endothelial growth factor.