Chung Sharon A, Xie Gang, Roshandel Delnaz, Sherva Richard, Edberg Jeffrey C, Kravitz Megan, Dellaripa Paul F, Hoffman Gary S, Mahr Alfred D, Seo Philip, Specks Ulrich, Spiera Robert F, St Clair E William, Stone John H, Plenge Robert M, Siminovitch Katherine A, Merkel Peter A, Monach Paul A
University of California, San Francisco, CA, USA.
Arthritis Rheum. 2012 Oct;64(10):3463-71. doi: 10.1002/art.34496.
To examine the association of previously identified autoimmune disease susceptibility loci with granulomatosis with polyangiitis (Wegener's) (GPA), and to determine whether the genetic susceptibility profiles of other autoimmune diseases are associated with those of GPA.
Genetic data from 2 cohorts were meta-analyzed. Genotypes for 168 previously identified single-nucleotide polymorphisms (SNPs) associated with susceptibility to different autoimmune diseases were ascertained in a total of 880 patients with GPA and 1,969 control subjects of European descent. Single-marker associations were identified using additive logistic regression models. Associations of multiple SNPs with GPA were assessed using genetic risk scores based on susceptibility loci for Crohn's disease, type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis (RA), celiac disease, and ulcerative colitis. Adjustment for population substructure was performed in all analyses, using ancestry-informative markers and principal components analysis.
Genetic polymorphisms in CTLA4 were significantly associated with GPA in the single-marker meta-analysis (odds ratio [OR] 0.79, 95% confidence interval [95% CI] 0.70-0.89, P = 9.8 × 10(-5) ). The genetic risk score for RA susceptibility markers was significantly associated with GPA (OR 1.05 per 1-unit increase in genetic risk score, 95% CI 1.02-1.08, P = 5.1 × 10(-5) ).
RA and GPA may arise from a similar genetic predisposition. Aside from CTLA4, other loci previously found to be associated with common autoimmune diseases were not statistically significantly associated with GPA in this study.
研究先前确定的自身免疫性疾病易感基因座与肉芽肿性多血管炎（韦格纳氏）（GPA）之间的关联，并确定其他自身免疫性疾病的遗传易感性特征是否与GPA的相关。
对2个队列的遗传数据进行荟萃分析。在总共880例GPA患者和1969例欧洲血统对照受试者中，确定了168个先前确定的与不同自身免疫性疾病易感性相关的单核苷酸多态性（SNP）的基因型。使用加性逻辑回归模型确定单标记关联。基于克罗恩病、1型糖尿病、系统性红斑狼疮、类风湿性关节炎（RA）、乳糜泻和溃疡性结肠炎的易感基因座，使用遗传风险评分评估多个SNP与GPA的关联。在所有分析中，使用祖先信息标记和主成分分析对人群亚结构进行调整。
在单标记荟萃分析中，CTLA4基因多态性与GPA显著相关（优势比[OR]0.79，95%置信区间[95%CI]0.70-0.89，P=9.8×10⁻⁵）。RA易感标记的遗传风险评分与GPA显著相关（遗传风险评分每增加1个单位，OR为1.05，95%CI为1.02-1.08，P=5.1×10⁻⁵）。
RA和GPA可能源于相似的遗传易感性。除CTLA4外，本研究中先前发现与常见自身免疫性疾病相关的其他基因座与GPA无统计学显著关联。
