Influence of polymorphisms in the vascular endothelial growth factor gene on allograft rejection after kidney transplantation: a meta-analysis.

Thanee Eiamsitrakoon,Adis Tasanarong,Noel Pabalan,Hamdi Jarjanazi,Phuntila Tharabenjasin

doi:10.12688/f1000research.27800.1

Abstract

Background: Reported associations of allograft rejection in kidney transplant patients with VEGF single nucleotide polymorphisms (SNPs) have been inconsistent between studies, which prompted a meta-analysis to obtain more precise estimates. Methods: Using the PICO elements, kidney transplant patients (P) were compared by genotype data between rejectors (I) and non-rejectors (C) in order to determine the risk of allograft rejection (O) attributed to the VEGF SNPs. Literature search of four databases yielded seven articles. To calculate risks for allograft rejection, four SNPs were examined.Using the allele-genotype model we compared the variant ( var) with the wild-type ( wt) and heterozygous ( var- wt) alleles. Meta-analysis treatments included outlier and subgroup analyses, the latter was based on ethnicity (Indians/Caucasians) and rejection type (acute/chronic). Multiple comparisons were corrected with the Bonferroni test. Results: Five highly significant outcomes (P a < 0.01) survived Bonferroni correction, one of which showed reduced risk for the var allele (OR 0.61, 95% CI 0.45-0.82). The remaining four indicated increased risk for the wt allele where the chronic rejection (OR 2.10, 95% CI 1.36-3.24) and Indian (OR 1.44, 95% CI 1.13-1.84) subgroups were accorded susceptibility status. Conclusions: Risk associations for renal allograft rejection were increased and reduced on account of the wt and var alleles, respectively. These findings could render the VEGF polymorphisms useful in the clinical genetics of kidney transplantation.

Highlights

Chronic kidney disease is a longstanding global health problem with substantial effects on morbidity and mortality[1]
Success of the transplanted organ or an allograft in the recipient is limited by graft rejection[3] which is characterized by inflammatory responses toward the graft tissue resulting in structural and functional impairments leading to allograft dysfunction[4]
Our study aims to provide better understanding of the genetic role of vascular endothelial growth factor (VEGF) single nucleotide polymorphism (SNP) on post-kidney transplantation (KT) allograft outcome in term of risk for allograft rejection among recipients, which might guide potential future directions in transplant genetics

Summary

Introduction

Chronic kidney disease is a longstanding global health problem with substantial effects on morbidity and mortality[1]. Differences in genetic background of transplant recipients are, in part, the cause of varying immune responses towards grafts[8] Recognizing these genetic differences and their effects on the immune response may help establish individualized immunosuppressive regimens that can improve allograft outcome[9]. This is accomplished by identifying the alleles that may increase risk or confer protection for immune-mediated complications after KT10. Conclusions: Risk associations for renal allograft rejection were increased and reduced on account of the wt and var alleles, respectively These findings could render the VEGF polymorphisms useful in the clinical genetics of kidney transplantation

Methods

Results

Discussion

Conclusion