Genetic Polymorphisms of Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) and clinical outcomes post-allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis

Clin Transplant. 2021 Aug;35(8):e14364. doi: 10.1111/ctr.14364. Epub 2021 Jun 13.

Abstract

Background and objective: Although HLA matching is considered as a key genetic predictor of allo-HSCT outcomes, genetic polymorphisms in non-HLA genes, especially in genes encoding immunoregulatory proteins, have also been proposed as additional risk factors linked to the occurrence of transplant complications. This study aimed to carry out a systematic review and meta-analysis from all eligible cohort studies to determine the effect of CTLA-4 gene polymorphisms, including rs231775, rs3087243, rs4553808, rs5742909, and rs733618, on clinical outcomes in patients receiving an allo-HSCT.

Methods: A systematic literature search in PubMed, Web of Science, and Scopus was performed to identify the relevant studies, and related information was extracted. The effect size (ES) and corresponding 95% confidence intervals (CIs) were calculated to estimate the association.

Results: 16 studies were eligible and included in the meta-analysis. The pooled results showed that only the dominant models of rs3087243 were significantly associated with chronic GVHD (cGVHD), while other SNPs were not significantly associated with overall survival, disease-free survival, relapse, and GVHD.

Conclusions: Our study represents, for the first time, a comprehensive meta-analysis on the role of CTLA-4 polymorphisms on outcomes after allo-HSCT. The results indicate that the CT60 CTLA-4 polymorphism could be a significant risk factor for cGVHD.

Keywords: CTLA-4; allo-HSCT; polymorphism.

Publication types

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

MeSH terms

  • CTLA-4 Antigen / genetics
  • Graft vs Host Disease* / genetics
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors

Substances

  • CTLA-4 Antigen