AUTHOR=Liu Weixi , Yang Zhicheng , Chen Yan , Yang Haoyu , Wan Xiaoxian , Zhou Xindie , Liu Ruiping , Zhang Yunkun 

TITLE=The Association Between CTLA-4, CD80/86, and CD28 Gene Polymorphisms and Rheumatoid Arthritis: An Original Study and Meta-Analysis

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.598076

DOI=10.3389/fmed.2021.598076

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> Rheumatoid arthritis (RA) is related to several pivotal susceptibility genes, including <italic>cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)</italic> and <italic>costimulatory molecule (CD80/CD86)</italic> genes. Although the connection between polymorphisms of <italic>CTLA-4</italic> and <italic>CD86</italic> genes in different populations of RA have been studied extensively, the results are controversial.</p><p><bold>Objective:</bold> To clarify the correlation in the Chinese Han population between <italic>CTLA-4, CD80/86</italic>, and <italic>CD28</italic> gene polymorphisms, and RA susceptibility.</p><p><bold>Methods:</bold> A case-control study (574 RA patients and 804 controls) was conducted to determine the correlation between <italic>CTLA-4</italic> rs231775 and rs16840252 gene polymorphisms, <italic>CD86</italic> rs17281995 gene polymorphisms, and the risk of RA for the Chinese Han population. Furthermore, an additional meta-analysis, including three single nucleotide polymorphisms (SNPs) (<italic>CTLA-4</italic> rs231775, <italic>CTLA-4</italic> rs3087243, and <italic>CTLA-4</italic> rs5742909) from 32 citations, including 43 studies, 24,703 cases and 23,825 controls was performed to elucidate the relationship between known SNPs in the <italic>CTLA-4</italic> genes and RA for more robust conclusions.</p><p><bold>Results:</bold> The results showed that <italic>CTLA-4</italic> rs231775 gene polymorphism decreased the RA risk (GA vs. AA, OR = 0.77, <italic>P</italic> = 0.025), whereas <italic>CTLA-4</italic> rs16840252 and <italic>CD86</italic> rs17281995 gene polymorphisms were not related to RA susceptibility. Stratification analyses by RF, ACPA, CRP, ESR, DAS28, and functional class identified significant associations for <italic>CTLA-4</italic> rs231775 and rs16840252 gene polymorphisms in the RF-positive and RF-negative groups. A meta-analysis of the literature on <italic>CTLA-4</italic> gene polymorphisms and RA risk revealed that the risk of RA was decreased by <italic>CTLA-4</italic> rs231775 gene polymorphisms.</p><p><bold>Conclusions:</bold> The <italic>CTLA-4</italic> rs231775 gene polymorphism decreased the risk of RA, whereas <italic>CTLA-4</italic> rs16840252 and <italic>CD86</italic> rs17281995 gene polymorphisms were not related to RA risk. A meta-analysis indicated that <italic>CTLA-4</italic> rs231775 and rs3087243 gene polymorphisms decreased the risk of RA. To support these analytical results, additional clinical cases should be investigated in further studies.</p>