Association of the STAT4 gene with increased susceptibility for some immune-mediated diseases
Association of the STAT4 gene with increased susceptibility for some immune-mediated diseases
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DOI：
10.1002/art.23792
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发表时间：
2008-09-01
影响因子：
--
通讯作者：
Urcelay, E.
中科院分区：
文献类型：
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作者：
Martinez, A.;Varade, J.;Urcelay, E.
Objective. STAT 4基因编码参与几种细胞因子的信号传导途径的转录因子，所述细胞因子包括白细胞介素-12（IL-12）、I型干扰素和IL-23。最近，STAT 4单倍型标记为rs7574865与类风湿性关节炎（RA）和系统性红斑狼疮的关联被报道。本研究的目的是探讨STAT 4标签多态性在其他免疫介导疾病中的作用。研究组包括2，776名连续招募的西班牙人：575名RA患者，440名多发性硬化症患者，700名炎症性肠病患者，311名I型糖尿病患者和723名种族匹配的健康对照受试者。STAT 4多态性rs7574865使用预先设计的TaqMan测定进行基因分型。采用卡方检验比较患者和对照组的等位基因和基因型频率。STAT 4多态性rs7574865与RA的关联在西班牙裔患者中得到验证（T与G，P = 1.2 × 10（-6），比值比[OR] 1.59，95%置信区间[95%CI] 1.31-1.92），并且首次在两种临床形式的炎症性肠病中描述了这种关联，克罗恩病和溃疡性结肠炎（T与G，P = 0.006，OR 1.29，95% CI 1.07-1.55）和1型糖尿病（T与G，P = 0.008，OR 1.36，95% CI 1.07-1.71）。与此相反，该多态性在多发性硬化患者和健康对照组中的基因型分布没有差异（T对G，P = 0.83，OR 1.02，95%CI 0.82-1.28）。STAT 4基因正在成为多种复杂疾病的一种新的常见风险因素。
Objective. The STAT4 gene encodes a transcription factor involved in the signaling pathways of several cytokines, including interieukin-12 (IL-12), the type I interferons, and IL-23. Recently, the association of a STAT4 haplotype marked by rs7574865 with rheumatoid arthritis (RA) and systemic lupus erythematosus was reported. The aim of this study was to investigate the role of this STAT4 tagging polymorphism in other immune-mediated diseases.Methods. The study group comprised 2,776 consecutively recruited Spanish individuals: 575 with RA, 440 with multiple sclerosis, 700 with inflammatory bowel disease, 311 with type I diabetes, and 723 ethnically matched healthy control subjects. The STAT4 polymorphism rs7574865 was genotyped using a predesigned TaqMan assay. Allele and genotype frequencies in patients and control subjects were compared by chi-square test.Results. The association of STAT4 polymorphism rs7574865 with RA was validated in patients of Spanish origin (for T versus G, P = 1.2 X 10(-6), odds ratio [OR] 1.59, 95% confidence interval [95% CI] 1.31-1.92), and the association was described for the first time in both clinical forms of inflammatory bowel disease, Crohn's disease and ulcerative colitis (for T versus G, P = 0.006, OR 1.29, 95% CI 1.07-1.55), and in type 1 diabetes mellitus (for T versus G, P = 0.008, OR 1,36, 95% CI 1.07-1.71). In contrast, the genotypic distribution of this polymorphism showed no difference between patients with multiple sclerosis and healthy control subjects (for T versus G, P = 0.83, OR 1.02, 95% CI 0.82-1.28).Conclusion. The STAT4 gene is emerging as a novel common risk factor for diverse complex diseases.