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

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...

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Main Authors: Weixi Liu, Zhicheng Yang, Yan Chen, Haoyu Yang, Xiaoxian Wan, Xindie Zhou, Ruiping Liu, Yunkun Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-02-01
Series:Frontiers in Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2021.598076/full
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author Weixi Liu
Zhicheng Yang
Yan Chen
Haoyu Yang
Xiaoxian Wan
Xindie Zhou
Ruiping Liu
Yunkun Zhang
author_facet Weixi Liu
Zhicheng Yang
Yan Chen
Haoyu Yang
Xiaoxian Wan
Xindie Zhou
Ruiping Liu
Yunkun Zhang
author_sort Weixi Liu
collection DOAJ
description 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.
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spelling doaj.art-7d93ea01924a491bbf9feeedc72441fa2022-12-21T22:21:10ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-02-01810.3389/fmed.2021.598076598076The Association Between CTLA-4, CD80/86, and CD28 Gene Polymorphisms and Rheumatoid Arthritis: An Original Study and Meta-AnalysisWeixi LiuZhicheng YangYan ChenHaoyu YangXiaoxian WanXindie ZhouRuiping LiuYunkun ZhangBackground: 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.https://www.frontiersin.org/articles/10.3389/fmed.2021.598076/fullrheumatoid arthritispolymorphismsCTLA-4CD80/86CD28meta-analysis
spellingShingle Weixi Liu
Zhicheng Yang
Yan Chen
Haoyu Yang
Xiaoxian Wan
Xindie Zhou
Ruiping Liu
Yunkun Zhang
The Association Between CTLA-4, CD80/86, and CD28 Gene Polymorphisms and Rheumatoid Arthritis: An Original Study and Meta-Analysis
Frontiers in Medicine
rheumatoid arthritis
polymorphisms
CTLA-4
CD80/86
CD28
meta-analysis
title The Association Between CTLA-4, CD80/86, and CD28 Gene Polymorphisms and Rheumatoid Arthritis: An Original Study and Meta-Analysis
title_full The Association Between CTLA-4, CD80/86, and CD28 Gene Polymorphisms and Rheumatoid Arthritis: An Original Study and Meta-Analysis
title_fullStr The Association Between CTLA-4, CD80/86, and CD28 Gene Polymorphisms and Rheumatoid Arthritis: An Original Study and Meta-Analysis
title_full_unstemmed The Association Between CTLA-4, CD80/86, and CD28 Gene Polymorphisms and Rheumatoid Arthritis: An Original Study and Meta-Analysis
title_short The Association Between CTLA-4, CD80/86, and CD28 Gene Polymorphisms and Rheumatoid Arthritis: An Original Study and Meta-Analysis
title_sort association between ctla 4 cd80 86 and cd28 gene polymorphisms and rheumatoid arthritis an original study and meta analysis
topic rheumatoid arthritis
polymorphisms
CTLA-4
CD80/86
CD28
meta-analysis
url https://www.frontiersin.org/articles/10.3389/fmed.2021.598076/full
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