Cytotoxic T-lymphocyte associated-protein-4 +49A/G-allele (rs231775) single nucleotide polymorphisms are associated with acute allograft renal transplantation rejection: A multilevel modelling of meta-analysis

Abstract

Background: Acute renal transplant rejection is believed to be an immunological phenomenon and is one of the most serious consequences of transplantation as a treatment for end-stage renal illness. In recent decades, numerous research has been conducted to investigate the relationship between cytotoxic T-lymphocyte antigen 4 +49A/G (CTLA-4 +49A/G) single nucleotide polymorphisms (SNPs) with the likelihood of rejection; nevertheless, the results are still controversial, and inconsistency has been documented among investigations. Consequently, the purpose of the present investigation was to conduct a study on the relation between CTLA-4 +49A/G polymorphism and risk of transplant rejection.  Methods: The study was reported based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Retrospective and prospective analytical randomized control trial (RCTs) published prints from Embase, PubMed, Cochrane, and Web of science were included to the study in accordance with the PRISMA guidelines. The search was conducted on February 2nd, 2022, using the search term (cytotoxic-T-lymphocyte-antigen-4 OR CTLA-4) AND (gene polymorphism OR single nucleotide polymorphisms OR allele OR alleles OR genotype OR genotypes) AND (renal OR kidney) AND (transplant OR transplantation) AND (acute rejection).  Results: The CTLA-4 G-allele/GG-genotype was more likely to be related to renal transplantation rejection risk. It was found with odds ratio (OR) in overall analysis of G vs. A-allele was 1.22 (95%CI 1.05-1.42; p-value=0.01) and the OR of GG vs. AG+AA-genotype was 1.47 (95%CI 1.14-1.89; p-value=0.003). However, the AA-genotype was not associated with renal transplantation rejection risk. The interesting finding in this study was the association of the SNPs and rejection of renal transplantation was especially found in Asian sub-analysis.  Conclusions: Consequently, the CTLA-4 G-allele/GG-genotype is related to the likelihood of rejection in patients underwent renal transplantation.