Association between CTLA4 gene polymorphisms and acute rejection of kidney transplantation: a meta-analysis

J Nephrol. 2012 Nov-Dec;25(6):996-1002. doi: 10.5301/jn.5000082.

Abstract

Objective: Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) has been shown to transmit an inhibitory signal to T cells, which is a therapeutic target for acute rejection of kidney transplantation, and CTLA4 polymorphisms have also been considered as a potential risk factor. However, major studies have not yielded significant results. Thus, we conducted a meta-analysis of existing studies to boost their statistical power to clarify any associations between CTLA4 gene polymorphisms and acute rejection of kidney transplantation.

Methods: We searched for studies using PubMed, Embase and Academic Source Premier databases and checked the reference lists of all included studies for other relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by both dominant and recessive genetic models.

Results: For CTLA4 +49A/G polymorphism, we found a marginally significant p value for A vs. G (OR=0.805, 95% CI, 0.677-0.957, p=0.014). No significant association between the -318C/T polymorphism and acute rejection risk was observed.

Conclusion: The results suggest that the CTLA4 gene +49A/G polymorphism may be a possible genetic susceptibility locus for acute rejection. The results of the present meta-analysis may be limited by a number of factors including inadequate total sample size and poor statistics, and should be interpreted with caution. Further confirmation in large and well-designed studies are needed.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Disease
  • CTLA-4 Antigen / genetics*
  • Genetic Predisposition to Disease
  • Graft Rejection / genetics*
  • Graft Rejection / immunology
  • Humans
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / immunology*
  • Models, Genetic
  • Odds Ratio
  • Phenotype
  • Polymorphism, Genetic*
  • Risk Factors

Substances

  • CTLA-4 Antigen
  • CTLA4 protein, human