Abstract
Background: Rheumatoid arthritis (RA) is related to several pivotal susceptibility genes, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and costimulatory molecule (CD80/CD86) genes. Although the connection between polymorphisms of CTLA-4 and CD86 genes in different populations of RA have been studied extensively, the results are controversial.Objective: To clarify the correlation in the Chinese Han population between CTLA-4, CD80/86, and CD28 gene polymorphisms, and RA susceptibility.Methods: A case-control study (574 RA patients and 804 controls) was conducted to determine the correlation between CTLA-4 rs231775 and rs16840252 gene polymorphisms, CD86 rs17281995 gene polymorphisms, and the risk of RA for the Chinese Han population. Furthermore, an additional meta-analysis, including three single nucleotide polymorphisms (SNPs) (CTLA-4 rs231775, CTLA-4 rs3087243, and CTLA-4 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 CTLA-4 genes and RA for more robust conclusions.Results: The results showed that CTLA-4 rs231775 gene polymorphism decreased the RA risk (GA vs. AA, OR = 0.77, P = 0.025), whereas CTLA-4 rs16840252 and CD86 rs17281995 gene polymorphisms were not related to RA susceptibility. Stratification analyses by RF, ACPA, CRP, ESR, DAS28, and functional class identified significant associations for CTLA-4 rs231775 and rs16840252 gene polymorphisms in the RF-positive and RF-negative groups. A meta-analysis of the literature on CTLA-4 gene polymorphisms and RA risk revealed that the risk of RA was decreased by CTLA-4 rs231775 gene polymorphisms.Conclusions: The CTLA-4 rs231775 gene polymorphism decreased the risk of RA, whereas CTLA-4 rs16840252 and CD86 rs17281995 gene polymorphisms were not related to RA risk. A meta-analysis indicated that CTLA-4 rs231775 and rs3087243 gene polymorphisms decreased the risk of RA. To support these analytical results, additional clinical cases should be investigated in further studies.
Highlights
Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent inflammation of the synovial membranes of joints and progressive cartilage damage, leading to severe joint deformity and loss of function [1]
T lymphocytes play an essential role in RA and their activation requires recognition of specific antigenic peptides by the T-cell receptor (TCR), and the co-stimulatory signals provided by accessory surface molecules on T cells [3]
The effects on RA risk of this single nucleotide polymorphism (SNP) were further evaluated according to the characteristics of rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (ACPA), C-reactive protein (CRP), erythrocyte
Summary
Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent inflammation of the synovial membranes of joints and progressive cartilage damage, leading to severe joint deformity and loss of function [1]. T lymphocytes play an essential role in RA and their activation requires recognition of specific antigenic peptides by the T-cell receptor (TCR), and the co-stimulatory signals provided by accessory surface molecules on T cells [3]. CTLA-4, a co-inhibitory receptor, is a member of the CD28 family expressed on the surface of T cells soon after its activation [3, 4]. CD80 and CD86 (B7 molecules), mainly expressed on B cells, monocytes/macrophages, and dendritic cells, are the ligands of CD28 and CTLA-4, which are upregulated when activated. Rheumatoid arthritis (RA) is related to several pivotal susceptibility genes, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and costimulatory molecule (CD80/CD86) genes. The connection between polymorphisms of CTLA-4 and CD86 genes in different populations of RA have been studied extensively, the results are controversial
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