Weersma Rinse K, Zhernakova Alexandra, Nolte Ilja M, Lefebvre Céline, Rioux John D, Mulder Flip, van Dullemen Hendrik M, Kleibeuker Jan H, Wijmenga Cisca, Dijkstra Gerard
Department of Gastroenterology and Hepatology, University Medical Center Groningen, The Netherlands.
Am J Gastroenterol. 2008 Mar;103(3):621-7. doi: 10.1111/j.1572-0241.2007.01660.x. Epub 2007 Nov 28.
Inflammatory bowel disease (IBD)--Crohn's disease (CD) and ulcerative colitis (UC)--and celiac disease are intestinal inflammatory disorders with a complex genetic background. Recently, two novel genes were found to be associated with IBD susceptibility. One, an uncommon coding variant (rs11209026) in the gene encoding for the interleukin-23 receptor (IL23R), conferred strong protection against CD. The other, rs2241880 in the autophagy-related 16-like 1 gene (ATG16L1), was associated with CD. We performed a case-control study for the association of IBD with IL23R and ATG16L1 in a Dutch cohort. We also looked at the association of IL23R and ATG16L1 with celiac disease.
Five hundred eighteen Dutch white IBD patients (311 CD and 207 UC, including 176 trios of patients with both parents), 508 celiac disease patients, and 893 healthy controls were studied for association with the rs11209026 (IL23R) and rs2241880 (ATG16L1) single nucleotide polymorphisms (SNP).
The rs11209026 SNP in IL23R had a protective effect for IBD in the case-control analysis (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.10-0.37, P= 6.6E-09). Both CD (OR 0.14, CI 0.06-0.37, P= 3.9E-07) and UC (OR 0.33, CI 0.15-0.73, P= 1.4E-03) were associated with IL23R. For ATG16L1, the rs2241880 SNP was associated with CD susceptibility (OR 1.36, CI 1.12-1.66, P= 0.0017). The population-attributable risk of carrying allele G is 0.24 and is 0.19 for homozygosity for allele G in CD. No association was found between IL23R or ATG16L1 and celiac disease.
We confirmed the association of IL23R and ATG16L1 with CD susceptibility and also the association of IL23R with UC. We found IL23R and ATG16L1 were not associated with celiac disease susceptibility.
炎症性肠病（IBD）——克罗恩病（CD）和溃疡性结肠炎（UC）——以及乳糜泻是具有复杂遗传背景的肠道炎症性疾病。最近，发现两个新基因与IBD易感性相关。一个是白细胞介素-23受体（IL23R）编码基因中的一个罕见编码变异（rs11209026），对CD具有很强的保护作用。另一个是自噬相关16样蛋白1基因（ATG16L1）中的rs2241880，与CD相关。我们在一个荷兰队列中进行了一项关于IBD与IL23R和ATG16L1关联的病例对照研究。我们还研究了IL23R和ATG16L1与乳糜泻的关联。
对518名荷兰白人IBD患者（311名CD患者和207名UC患者，包括176名父母均患病的三联体患者）、508名乳糜泻患者和893名健康对照者进行了rs11209026（IL23R）和rs2241880（ATG16L1）单核苷酸多态性（SNP）关联研究。
在病例对照分析中，IL23R中的rs11209026 SNP对IBD具有保护作用（优势比[OR]0.19，95%置信区间[CI]0.10 - 0.37，P = 6.6E - 09）。CD（OR 0.14，CI 0.06 - 0.37，P = 3.9E - 07）和UC（OR 0.33，CI 0.15 - 0.73，P = 1.4E - 03）均与IL23R相关。对于ATG16L1，rs2241880 SNP与CD易感性相关（OR 1.36，CI 1.12 - 1.66，P = 0.0017）。携带等位基因G的人群归因风险为0.24，在CD中纯合子等位基因G的风险为0.19。未发现IL23R或ATG16L1与乳糜泻之间存在关联。
我们证实了IL23R和ATG16L1与CD易感性相关，以及IL23R与UC相关。我们发现IL23R和ATG16L1与乳糜泻易感性无关。
