Roberts Rebecca L, Gearry Richard B, Hollis-Moffatt Jade E, Miller Allison L, Reid Julia, Abkevich Victor, Timms Kirsten M, Gutin Alexander, Lanchbury Jerry S, Merriman Tony R, Barclay Murray L, Kennedy Martin A
Department of Pathology, University of Otago, Christchurch School of Medicine & Health Sciences, Christchurch, New Zealand.
Am J Gastroenterol. 2007 Dec;102(12):2754-61. doi: 10.1111/j.1572-0241.2007.01525.x. Epub 2007 Sep 25.
Recently, separate genome-wide association analyses have identified nonsynonymous SNPs in IL23R and ATG16L1 (rs11209026; c1142G>A, R381Q, and rs2241880; c1338A>G, T300A, respectively) as strong candidate susceptibility factors for Crohn's disease (CD) in whites. The aim of our study was to test whether these SNPs are associated with CD in a population-based cohort of New Zealand Caucasian inflammatory bowel disease (IBD) patients.
Allele frequencies of rs11209026 and rs2241880 were determined in 496 CD patients, 466 ulcerative colitis (UC) patients, and 591 controls. Distribution of the relevant alleles was compared between controls and IBD patients. rs11209026 and rs2241880 genotype distributions were examined both within IBD clinical subphenotypes and CARD15 genotypes.
rs11209026 and rs2241880 were both associated with CD (P valuers11209026=0.0026, OR 0.54, 95% CI 0.36-0.81; P valuers2241880=0.0001, OR 1.41, 95% CI 1.18-1.67). In addition, there was evidence for association of rs11209026 with UC (P value=0.037, OR 0.66, 95% CI 0.45-0.98). No significant association was observed between IL23R genotype or ATG16L1 genotype and IBD subphenotypes. IL23R was associated with CD and UC only in the absence of CARD15 mutations, whereas ATG16L1 was associated with CD in the presence and absence of CARD15 mutations.
We replicated the previously reported associations between CD and rs11209026 and rs2241880, confirming that IL23R and ATG16L1 are susceptibility loci for CD in the New Zealand population. We also provide further evidence for association of rs11209026 with UC and a report of an additive effect between IL23R and CARD15 genotypes in CD.
最近，单独的全基因组关联分析已确定白细胞介素23受体（IL23R）和自噬相关16样蛋白1（ATG16L1）中的非同义单核苷酸多态性（SNP）（分别为rs11209026；c1142G>A，R381Q，以及rs2241880；c1338A>G，T300A）是白人克罗恩病（CD）强有力的候选易感因素。我们研究的目的是检测这些SNP在以人群为基础的新西兰白种人炎症性肠病（IBD）患者队列中是否与CD相关。
测定了496例CD患者、466例溃疡性结肠炎（UC）患者及591例对照者中rs11209026和rs2241880的等位基因频率。比较了对照者与IBD患者之间相关等位基因的分布情况。在IBD临床亚表型和CARD15基因型中检测了rs11209026和rs2241880的基因型分布。
rs11209026和rs2241880均与CD相关（P值rs11209026 = 0.0026，比值比0.54，95%可信区间0.36 - 0.81；P值rs2241880 = 0.0001,比值比1.41，95%可信区间1.18 - 1.67）。此外，有证据表明rs11209026与UC相关（P值 = 0.037，比值比0.66，95%可信区间0.45 - 0.98）。未观察到IL23R基因型或ATG16L1基因型与IBD亚表型之间存在显著关联。IL23R仅在不存在CARD15突变时与CD和UC相关，而ATG16L1在存在和不存在CARD15突变时均与CD相关。
我们重复了先前报道的CD与rs11209026和rs2241880之间的关联，证实IL23R和ATG16L1是新西兰人群中CD的易感基因座。我们还提供了rs11209026与UC相关的进一步证据，以及一份关于IL23R和CARD15基因型在CD中存在累加效应的报告。
