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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.

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