Table_2_Association of NLRP3 rs35829419 and rs10754558 Polymorphisms With Risks of Autoimmune Diseases: A Systematic Review and Meta-Analysis.docx

The existing knowledge about the association between NLRP3 rs35829419/rs10754558 polymorphisms and susceptibility to autoimmune diseases (AIDs) remains controversial. Herein, a meta-analysis was performed to evaluate such association. We searched databases for relevant studies published in English up to February 2021. Stata14 was used to assess the odds ratio (OR). As for NLRP3 rs35829419, no significant association to overall AIDs was found in three genetic models [A vs. C: OR (95%CI) = 0.89 (0.69–1.14); AC vs. CC: 1.00 (0.77–1.30); AA/AC vs. CC: 0.93 (0.71–1.20)]. However, subgroup analysis by disease type showed that NLRP3 rs35829419 A allele may have a significant protective effect on rheumatoid arthritis (RA) susceptibility [A vs. C: 0.74 (0.57–0.96)]. NLRP3 rs10754558 polymorphism contributes to significantly reduce the risk of AIDs in the allelic model [G vs. C: 0.78 (0.71–0.87)], homozygote co-dominant model [GG vs. CC: 0.63 (0.51–0.77)], heterozygote co-dominant model [GC vs. CC: 0.78 (0.66–0.91)], dominant model [GG/GC vs. CC: 0.73 (0.63–0.84)], and recessive model [GG vs. GC/CC: 0.73 (0.62–0.88)]. In the subgroup analysis by ethnicity, association was observed between the NLRP3 rs10754558 G allele and AIDs in Latin Americans, but not in European, Arabian, or Asian populations. Stratification by disease type showed a significant association of the NLRP3 rs10754558 G allele with type 1 diabetes (T1D), RA, and systemic lupus erythematosus (SLE), but not with celiac disease (CD), multiple sclerosis (MS), or myasthenia gravis (MG). This meta-analysis suggests that the NLRP3 rs10754558, but not rs35829419, polymorphism is associated with susceptibility to AIDs, especially in Latin American individuals.

目前关于NLRP3 rs35829419/rs10754558基因多态性与自身免疫性疾病（autoimmune diseases, AIDs）易感性之间的关联，现有研究结论尚存争议。本研究通过荟萃分析（meta-analysis）对该关联展开评估：我们检索了截至2021年2月发表的全部英文相关研究文献，并采用Stata14软件计算比值比（odds ratio, OR）。针对NLRP3 rs35829419位点，在三种遗传模型下均未发现其与总体自身免疫性疾病存在显著关联[等位基因模型A vs. C：OR(95%置信区间, 95%CI)=0.89(0.69~1.14)；杂合子共显性模型AC vs. CC：1.00(0.77~1.30)；显性模型AA/AC vs. CC：0.93(0.71~1.20)]。但按疾病类型进行亚组分析后发现，NLRP3 rs35829419位点的A等位基因对类风湿关节炎（rheumatoid arthritis, RA）易感性具有显著保护作用[A vs. C：0.74(0.57~0.96)]。而NLRP3 rs10754558基因多态性在多种遗传模型下均可显著降低自身免疫性疾病的发病风险：等位基因模型G vs. C：0.78(0.71~0.87)；纯合子共显性模型GG vs. CC：0.63(0.51~0.77)；杂合子共显性模型GC vs. CC：0.78(0.66~0.91)；显性模型GG/GC vs. CC：0.73(0.63~0.84)；隐性模型GG vs. GC/CC：0.73(0.62~0.88)。按种族进行亚组分析显示，NLRP3 rs10754558位点的G等位基因与自身免疫性疾病的关联仅在拉丁美洲人群中显著，而在欧洲、阿拉伯及亚洲人群中未观察到该关联。按疾病类型分层分析则显示，NLRP3 rs10754558位点的G等位基因与1型糖尿病（type 1 diabetes, T1D）、类风湿关节炎（RA）及系统性红斑狼疮（systemic lupus erythematosus, SLE）的易感性显著相关，但与乳糜泻（celiac disease, CD）、多发性硬化（multiple sclerosis, MS）及重症肌无力（myasthenia gravis, MG）无显著关联。本项荟萃分析表明，NLRP3 rs10754558基因多态性（而非rs35829419）与自身免疫性疾病易感性相关，尤其在拉丁美洲人群中更为显著。