Polymorphisms in the cytotoxic T-lymphocyte antigen 4 gene and acute rejection risk in transplant recipients

Abstract

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene polymorphisms have been reported to influence the risk for acute rejection (AR) in transplant recipients. However, the results still remain controversial and ambiguous. The objective of the current study was to conduct a meta-analysis investigating the association between polymorphisms in the CTLA-4 gene and the risk of AR in transplant recipients. Electronic searches for all publications were conducted on associations between this variant and acute rejection in Medline and Embase databases through November 2011. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to estimate the strength of the association. Three polymorphisms (+49 adenine/guanine [+49A/G], -318 cytosine/thymine [-318C/T], and the +6230G/A polymorphism [CT60]) in 18 case-control studies from ten articles were analyzed. This meta-analysis included 2,081 cases of transplant recipients in which 813 cases developed AR and 1,268 cases did not develop AR. The results indicated that there was no statistically significant association between the risk of AR and the +49A/G polymorphism or the -318C/T polymorphism (+49A/G: OR = 0.876, 95 % CI = 0.650-1.180 for GG vs. AA; OR = 1.121, 95 % CI = 0.911-1.379 for AG + GG vs. AA; -318C/T: OR = 0.397, 95 % CI = 0.138-1.143 for TT vs. CC; OR = 0.987, 95 %CI = 0.553-1.760 for CT + TT vs. CC). However, individuals who carried CT60 A allele might have a decreased risk of AR (AA vs. GG OR = 0.535, 95 % CI = 0.340-0.841, A vs. G OR = 0.759, 95 % CI = 0.612-0.914) in liver transplant recipients among Europeans, but because only two studies were included, so the result should be caution. In further stratified analyses for the +49A/G and the -318C/T polymorphisms, no obvious significant associations were found in subgroups of renal transplant recipients and Europeans, a reduced incidence of acute rejection was observed in liver transplant recipients that are homogenous for +49G (OR = 0.638, 95 % CI = 0.427-0.954 for GG vs. AA/AG), while this has not been observed in renal transplant recipients. Overall this meta-analysis suggests that +49A/G and the -318C/T polymorphisms in CTLA-4 may be not associated with the risk of rejection after organ transplantation, but CTLA +49A/G and +6230G/A polymorphisms may be associated with acute rejection after liver transplantation, not after renal transplantation. In future, more studies should be included to evaluate the association between +6230G/A polymorphism and AR risk.

The influence of CTLA‐4 single nucleotide polymorphisms on acute kidney allograft rejection in Turkish patients

“…The other area of interest, +49A/G, is found in exon‐1, gene polymorphisms in this site may change the cell surface expression of CTLA‐4 and have shown to be related to autoimmune disorders . In our study, we found + 49A/G genotype and G allelic variant to be unrelated to acute rejection risk, in harmony with a recent meta‐analysis that revealed no relations in most studies . The exceptions are the findings of Gendzekhadze et al.…”

A deeper understanding of the association betweenCTLA4+49A/G and acute rejection in renal transplantation: an updated meta-analysis

“…However, these studies have yielded inconsistent results. 13,14 To produce more precise results, we evaluated these associations using a meta-analysis.…”

A risk assessment model of acute liver allograft rejection by genetic polymorphism of CD276

“…Although the development of acute rejection is complicated, its initiation requires both allorecognition and T‐cell activation (Ingulli, ; Wood & Goto, ). Genetic polymorphisms of MHC, costimulatory molecules, and cytokines genes, which involve in the allorecognition and the activation, have been proved to be associated with acute rejection in liver and renal transplantations (Bitetto et al., ; Jiang et al., ; Tapirdamaz et al., ; Zhu, Huang, Liu, & Xie, ).…”