Confirmation of an association between rs6822844 at the Il2-Il21 region and multiple autoimmune diseases: evidence of a general susceptibility locus.
Confirmation of an association between rs6822844 at the Il2-Il21 region and multiple autoimmune diseases: evidence of a general susceptibility locus.
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DOI：
10.1002/art.27222
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发表时间：
2010-02
影响因子：
--
通讯作者：
Nath, Swapan K.
中科院分区：
文献类型：
--
作者：
Maiti, Amit K.;Kim-Howard, Xana;Viswanathan, Parvathi;Guillen, Laura;Rojas-Villarraga, Adriana;Deshmukh, Harshal;Direskeneli, Haner;Saruhan-Direskeneli, Gueher;Canas, Carlos;Tobon, Gabriel J.;Sawalha, Amr H.;Chernavsky, Alejandra C.;Anaya, Juan-Manuel;Nath, Swapan K.
自身免疫性疾病通常具有共同的易感基因，表明相似的分子机制。越来越多的证据表明，rs6822844在IL 2-IL 21区域与欧洲血统的个体中的多种自身免疫性疾病密切相关。本研究试图在非欧洲人群中复制rs6822844与6种不同免疫介导疾病之间的关联，并使用先前发表的研究数据进行疾病特异性和总体荟萃分析。我们评估了阿根廷受试者中rs6822844与乳糜泻（CD）之间的病例对照关系;哥伦比亚受试者中rs6822844与类风湿性关节炎（RA）、1型糖尿病（DM）、原发性干燥综合征（SS）和系统性红斑狼疮（SLE）之间的病例对照关系;土耳其受试者中rs6822844与白塞病（BD）之间的病例对照关系。比较病例组和对照组的等位基因和基因分布。使用本研究和既往研究的数据进行荟萃分析。我们检测到rs6822844与SLE（P = 0.008）、1型DM（P = 0.014）、RA（P = 0.019）和原发性SS（P = 0.033）显著相关，但与BD（P = 0.34）或CD（P = 0.98）无关。我们发现很少的证据表明，人口分化（FST = 0.01）的情况下，从阿根廷和哥伦比亚的控制，这表明该协会是不受人口结构。疾病特异性荟萃分析显示RA（Pmeta = 3.61 × 10-6）、炎症性肠病（IBD;克罗恩病和溃疡性结肠炎）（Pmeta = 3.48 × 10-12）、1型糖尿病（Pmeta = 5.33 × 10-5）和CD（Pmeta = 5.30 × 10-3）显著相关。所有自身免疫性疾病的总体荟萃分析加强了与rs6822844的相关性（23个数据集; Pmeta = 2.61 × 10-25，比值比0.73 [95%置信区间0.69-0.78]）。我们的研究结果表明，rs6822844与非欧洲人群中的多种自身免疫性疾病之间存在关联。荟萃分析结果强烈地加强了欧洲和非欧洲人群中多种自身免疫性疾病之间的这种强有力的关联。
Autoimmune diseases often have susceptibility genes in common, indicating similar molecular mechanisms. Increasing evidence suggests that rs6822844 at the IL2–IL21 region is strongly associated with multiple autoimmune diseases in individuals of European descent. This study was undertaken to attempt to replicate the association between rs6822844 and 6 different immune-mediated diseases in non-European populations, and to perform disease-specific and overall meta-analyses using data from previously published studies. We evaluated case–control associations between rs6822844 and celiac disease (CD) in subjects from Argentina; rheumatoid arthritis (RA), type 1 diabetes mellitus (DM), primary Sjögren's syndrome (SS), and systemic lupus erythematosus (SLE) in subjects from Colombia; and Behçet's disease (BD) in subjects from Turkey. Allele and gene distributions were compared between cases and controls. Meta-analyses were performed using data from the present study and previous studies. We detected significant associations of rs6822844 with SLE (P = 0.008), type 1 DM (P = 0.014), RA (P = 0.019), and primary SS (P = 0.033) but not with BD (P = 0.34) or CD (P = 0.98). We identified little evidence of population differentiation (FST = 0.01) within cases and controls from Argentina and Colombia, suggesting that association was not influenced by population substructure. Disease-specific meta-analysis indicated significant association for RA (Pmeta = 3.61 × 10–6), inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) (Pmeta = 3.48 × 10–12), type 1 DM (Pmeta = 5.33 × 10–5), and CD (Pmeta = 5.30 × 10–3). Overall meta-analysis across all autoimmune diseases reinforced association with rs6822844 (23 data sets; Pmeta = 2.61 × 10–25, odds ratio 0.73 [95% confidence interval 0.69–0.78]). Our results indicate that there is an association between rs6822844 and multiple auto-immune diseases in non-European populations. Meta-analysis results strongly reinforce this robust association across multiple autoimmune diseases in both European-derived and non-European populations.
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