STAT3 locus in inflammatory bowel disease and multiple sclerosis susceptibility
STAT3 locus in inflammatory bowel disease and multiple sclerosis susceptibility
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DOI：
10.1038/gene.2010.10
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发表时间：
2010-04-01
影响因子：
5
通讯作者：
Urcelay, E.
中科院分区：
文献类型：
--
作者：
Cenit, M. C.;Alcina, A.;Urcelay, E.
STAT 3（信号转导和转录激活因子3）信号传导是Th 17依赖性自身免疫过程的关键组分。全基因组关联研究（GWAS）已经揭示了STAT 3基因在炎症性肠病（IBD）易感性中的作用，尽管临床亚表型的确认是必要的。在T细胞中靶向缺失Stat 3的小鼠对实验性自身免疫性脑脊髓炎具有抗性，这是一种多发性硬化症（MS）模型。此外，在从临床孤立综合征演变为确定的MS的患者和复发患者的T细胞中报告了磷酸化STAT 3增加。这些证据使我们分析了STAT 3在克罗恩病（CD）、溃疡性结肠炎（UC）和MS风险中的作用。在STAT 3区域的多态性（rs3809758/rs744166/rs 1026916/rs 12948909）进行基因分型，并推断单倍型，随后在860 IBD和1540 MS西班牙患者和1720种族匹配的对照进行了分析。每个多态性的风险等位基因所确定的单倍型与IBD的两种临床表型显著相关（CD：P=0.005，比值比1.25，95%置信区间1.06-1.46; UC：P=0.002，比值比1.19，95%置信区间1.02-1.38）。在一个独立的人群中，最初描述的IBD与STAT 3多态性的相关性在CD和UC两种临床表型中得到证实。该基因在MS中的主要作用似乎不太可能。Genes and Immunity（2010）11，264-268; doi：10.1038/gene.2010.10; 2010年3月4日在线发表
STAT3 (signal transducer and activator of transcription 3) signaling is a critical component of Th17-dependent autoimmune processes. Genome-wide association studies (GWAS) have revealed the role of the STAT3 gene in inflammatory bowel disease (IBD) susceptibility, although confirmation in clinical subphenotypes is warranted. Mice with targeted deletion of Stat3 in T cells are resistant to experimental autoimmune encephalomyelitis, which is a multiple sclerosis (MS) model. Moreover, increased phosphorylated STAT3 was reported in T cells of patients evolving from clinically isolated syndrome to defined MS and in relapsing patients. These evidences led us to analyze the role of STAT3 in Crohn's disease (CD), ulcerative colitis (UC) and MS risk. Polymorphisms in the STAT3 region (rs3809758/rs744166/rs1026916/rs12948909) were genotyped and the inferred haplotypes were subsequently analyzed in 860 IBD and 1540 MS Spanish patients and 1720 ethnically matched controls. The haplotype conformed by the risk alleles of each polymorphism was significantly associated with both clinical phenotypes of IBD (CD: P=0.005, odds ratio 1.25, 95% confidence interval 1.06-1.46; and UC: P=0.002, odds ratio 1.19, 95% confidence interval 1.02-1.38). No evidence of association was detected for MS. The originally described association of IBD with STAT3 polymorphisms is corroborated for the two clinical phenotypes, CD and UC, in an independent population. A major role of this gene in MS seems unlikely. Genes and Immunity (2010) 11, 264-268; doi:10.1038/gene.2010.10; published online 4 March 2010