Lee Young Ho, Song Gwan Gyu
Department of Rheumatology, Korea University College of Medicine, Seoul, Republic of Korea.
Public Health Genomics. 2022 Sep 12:1-11. doi: 10.1159/000526212.
The tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene produces ubiquitin-editing protein A20, which inhibits nuclear factor-κB (NF-κB) activation in a variety of signaling pathways. We examined the association between TNFAIP3 polymorphisms and rheumatoid arthritis (RA) susceptibility.
MEDLINE, Embase, Scopus, and Web of Science were searched for available articles on TNFAIP3 polymorphisms in RA patients from inception until July 11, 2022. We included case-control studies on the association between rs2230926 and rs5029937 polymorphisms of TNFAIP3 and RA, and we excluded studies that contained overlapping data. We scored the quality of each study included based on the Newcastle-Ottawa Scale. Meta-analyses evaluated the association between TNFAIP3 polymorphisms and RA susceptibility in diverse ethnic populations and was verified through trial sequential analysis (TSA). This meta-analysis was registered in the PROSPERO register (number: CRD42022345160). There was no funding source.
Seventeen studies were chosen for meta-analysis. Ten studies for rs2230926, and seven for rs5029937. An association was noted between TNFAIP3 rs2230926 G allele and RA in all subjects (odds ratio [OR] = 1.389; 95% confidence interval [CI] = 1.161-1.662; p < 0.001). Ethnicity-specific analysis showed significant association of rs2230926 G allele with RA in Europeans and Asians (OR = 1.642; 95% CI = 1.099-2.452; p = 0.015; OR = 1.404; 95% CI = 1.262-1.562; p < 0.001). An association was also noted between TNFAIP3 rs5029937 T allele and RA in all subjects (OR = 1.389; 95% CI = 1.207-1.785; p < 0.001). An ethnicity-specific meta-analysis revealed a significant association of the rs5029937 T allele with RA in Europeans and Asians. Dominant model analysis showed the same pattern for TNFAIP3 rs2230926 G and rs5029937 T alleles in Europeans and Asians, suggesting an association between rs2230926 G and rs5029937. TSA indicated a robust association between the TNFAIP3 polymorphisms and the risk of RA.
TNFAIP3 rs2230926 and rs5029937 polymorphisms are associated with RA susceptibility in European and Asian populations. However, the data were not stratified by parameters such as rheumatoid factor status, disease activity, or environmental variables.
肿瘤坏死因子α诱导蛋白3（TNFAIP3）基因产生泛素编辑蛋白A20，其在多种信号通路中抑制核因子κB（NF-κB）激活。我们研究了TNFAIP3基因多态性与类风湿关节炎（RA）易感性之间的关联。
检索MEDLINE、Embase、Scopus和Web of Science数据库，查找自数据库建立至2022年7月11日有关RA患者中TNFAIP3基因多态性的可用文章。我们纳入了关于TNFAIP3基因rs2230926和rs5029937多态性与RA关联的病例对照研究，并排除了包含重叠数据的研究。我们根据纽卡斯尔-渥太华量表对纳入的每项研究质量进行评分。荟萃分析评估了TNFAIP3基因多态性与不同种族人群RA易感性之间的关联，并通过序贯试验分析（TSA）进行验证。该荟萃分析已在PROSPERO注册库中注册（编号：CRD42022345160）。本研究无资金来源。
17项研究被纳入荟萃分析。其中10项研究涉及rs2230926，7项研究涉及rs5029937。在所有受试者中，发现TNFAIP3基因rs2230926的G等位基因与RA存在关联（优势比[OR]=1.389；95%置信区间[CI]=1.161-1.662；p<0.001）。种族特异性分析显示，rs2230926的G等位基因在欧洲人和亚洲人中与RA显著相关（OR=1.642；95%CI=1.099-2.452；p=0.015；OR=1.404；95%CI=1.262-1.562；p<0.001）。在所有受试者中，还发现TNFAIP3基因rs5029937的T等位基因与RA存在关联（OR=1.389；95%CI=1.207-1.785；p<0.001）。种族特异性荟萃分析显示，rs5029937的T等位基因在欧洲人和亚洲人中与RA显著相关。显性模型分析显示，在欧洲人和亚洲人中，TNFAIP3基因rs2230926的G等位基因和rs5029937的T等位基因呈现相同模式，提示rs2230926的G等位基因与rs5029937之间存在关联。TSA表明TNFAIP3基因多态性与RA风险之间存在显著关联。
TNFAIP3基因rs2230926和rs5029937多态性与欧洲和亚洲人群的RA易感性相关。然而，数据未按类风湿因子状态、疾病活动度或环境变量等参数进行分层。
