Association of four CTLA-4 gene polymorphisms with pemphigus risk: a systematic review, meta-analysis, and meta-regression

Objectives This review aimed to summarize the existing data on the contribution of four single nucleotide polymorphisms (SNPs) in the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) genes to pemphigus susceptibility. Methods An electronic literature search for eligible studies among those published prior to 30 April 2024 was conducted through the PubMed, EMBASE, Web of Science, and Scopus databases. To minimize publication bias, an additional search was performed via the Google Scholar and Semantic Scholar search engines. Meta-analyses, together with subgroup analyses and meta-regressions, were performed for the following four CTLA-4 SNPs: rs231775, rs5742909, rs3087243, and rs733618. Results Combined analyses revealed a significant increase in pemphigus risk conferred by the CTLA-4 rs5742909*C and rs733618*C alleles. Conversely, there was no evidence of any significant association between the rs231775*G and rs3087243*G alleles and susceptibility to pemphigus. Subgroup analyses by ethnicity and pemphigus type (vulgaris or foliaceus) and meta-regressions did not reveal any significant difference. Conclusion This meta-analysis suggested that two of the four investigated CTLA-4 SNPs were significantly associated with increased pemphigus risk. Registration: This review has been registered on PROSPERO: CRD42024550668; available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024550668