Festen E A M, Goyette P, Scott R, Annese V, Zhernakova A, Lian J, Lefèbvre C, Brant S R, Cho J H, Silverberg M S, Taylor K D, de Jong D J, Stokkers P C, Mcgovern D, Palmieri O, Achkar J-P, Xavier R J, Daly M J, Duerr R H, Wijmenga C, Weersma R K, Rioux J D
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Gut. 2009 Jun;58(6):799-804. doi: 10.1136/gut.2008.166918. Epub 2009 Feb 6.
Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac disease, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus and psoriasis), while the roles that interleukin 2 (IL2) and IL21 play in the immune response also make them attractive candidates for IBD. The objective of this study was to test for association between the IL2/IL21 locus and the IBDs.
The four single nucleotide polymorphisms (SNPs) in the IL2/IL21 locus most associated with coeliac disease were genotyped in 1590 subjects with IBD and 929 controls from The Netherlands, and then replicated in a North American cohort (2387 cases and 1266 controls) and an Italian cohort (805 cases and 421 controls), yielding a total of 4782 cases (3194 UC, 1588 CD) and 2616 controls. Allelic association testing and a pooled analysis using a Cochran-Mantel-Haenszel test were performed.
All four SNPs were strongly associated with UC in all three cohorts and reached genome-wide significance in the pooled analysis (rs13151961 p = 1.35 x 10(-10), rs13119723 p = 8.60 x 10(-8), rs6840978 p = 3.0 7x 10(-8), rs6822844 p = 2.77 x 10(-9)). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86 x 10(-5)).
A strong association for the IL2/IL21 locus with UC was found, which also confirms it as a general susceptibility locus for inflammatory disease.
已知遗传易感性在克罗恩病（CD）和溃疡性结肠炎（UC）这两种炎症性肠病（IBD）的易感性中起很大作用。已知4q27上的IL2/IL21基因座是炎症性疾病的常见风险基因座（在乳糜泻、1型糖尿病、类风湿性关节炎、系统性红斑狼疮和牛皮癣中已得到证实），而白细胞介素2（IL2）和IL21在免疫反应中的作用也使它们成为IBD的有吸引力的候选因素。本研究的目的是检测IL2/IL21基因座与IBD之间的关联。
对来自荷兰的1590例IBD患者和929例对照进行了IL2/IL21基因座中与乳糜泻最相关的四个单核苷酸多态性（SNP）的基因分型，然后在北美队列（2387例病例和1266例对照）和意大利队列（805例病例和421例对照）中进行重复验证，总共得到4782例病例（3194例UC，1588例CD）和2616例对照。进行了等位基因关联测试，并使用 Cochr an-Mantel-Haenszel 检验进行了汇总分析。
在所有三个队列中，所有四个SNP均与UC密切相关，并在汇总分析中达到全基因组显著性（rs13151961 p = 1.35 x 10(-10)，rs13119723 p = 8.60 x 10(-8)，rs6840978 p = 3.07 x 10(-8)，rs6822844 p = 2.77 x 10(-9)）。在汇总分析中还发现与CD存在中度关联（p值范围为0.0016 - 9.86 x 10(-5)）。
发现IL2/IL21基因座与UC存在强关联，这也证实了它是炎症性疾病的一个普遍易感基因座。
