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

Rheumatoid arthritis (RA) is related to several pivotal susceptibility genes, including and genes. Although the connection between polymorphisms of and genes in different populations of RA have been studied extensively, the results are controversial. To clarify the correlation in the Chinese Han population between , and gene polymorphisms, and RA susceptibility. A case-control study (574 RA patients and 804 controls) was conducted to determine the correlation between rs231775 and rs16840252 gene polymorphisms, rs17281995 gene polymorphisms, and the risk of RA for the Chinese Han population. Furthermore, an additional meta-analysis, including three single nucleotide polymorphisms (SNPs) ( rs231775, rs3087243, and 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 genes and RA for more robust conclusions. The results showed that rs231775 gene polymorphism decreased the RA risk (GA vs. AA, OR = 0.77, = 0.025), whereas rs16840252 and rs17281995 gene polymorphisms were not related to RA susceptibility. Stratification analyses by RF, ACPA, CRP, ESR, DAS28, and functional class identified significant associations for rs231775 and rs16840252 gene polymorphisms in the RF-positive and RF-negative groups. A meta-analysis of the literature on gene polymorphisms and RA risk revealed that the risk of RA was decreased by rs231775 gene polymorphisms. The rs231775 gene polymorphism decreased the risk of RA, whereas rs16840252 and rs17281995 gene polymorphisms were not related to RA risk. A meta-analysis indicated that rs231775 and rs3087243 gene polymorphisms decreased the risk of RA. To support these analytical results, additional clinical cases should be investigated in further studies.