► Yadav P, Ellinghaus D, Rémy G, et al. Genetic factors interact with tobacco smoke to modify risk for inflammatory bowel disease in humans and mice. Gastroenterology 2017;153:550– 565. The relationship between smoking and IBD risk is unclear. Gene– smoking interactions in IBD were explored at a genome-wide level in this paper using data from the International IBD Genetics Consortium. Immunochip custom array data from 20 000 IBD cases were compared with control cases in a meta-analysis of smokers versus non-smokers. Sixty-four single nucleotide polymorphisms (SNPs) were identified for which the associated risk of IBD was affected by smoking. Nearly half of these SNPs were close to SNPs known to be related to IBD, and many were located near genes linked with mucosal barrier regulation and immune response. Twenty SNPs were within the human leucocyte antigen region at 6p21, so the effect on adaptive immunity may be an explanation for the gene–smoking interaction. Seven SNPs interacted with smoking in opposite directions in Crohn’s disease and UC. There was also a contrast between former, ever and current smokers. Two genes identified as potentially interacting with smoking, Il10 and Nod2, were evaluated in genetic knockout mouse models exposed to smoke in ventilated smoking chambers, equivalent to five cigarettes per day for 8 weeks. Il10-deficient mice developed accelerated colitis as well as ileitis. Nod2-deficient mice developed ileitis. In wild type mice exposed to smoke, there was no sign of IBD. Hence, there is a protective role of Il10 and Nod2 in response to smoking and may have a role in disease location. In summary, the effect of smoking in the pathogenesis of IBD depends on patient-specific genetic variants.

中文翻译：

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文献中的 GI 亮点

► Yadav P、Ellinghaus D、Rémy G 等。遗传因素与烟草烟雾相互作用以改变人类和小鼠炎症性肠病的风险。Gastroenterology 2017;153:550-565. 吸烟与 IBD 风险之间的关系尚不清楚。本文使用国际 IBD 遗传学联盟的数据，在全基因组水平上探讨了 IBD 中基因与吸烟的相互作用。在吸烟者与非吸烟者的荟萃分析中，将来自 20 000 名 IBD 病例的免疫芯片定制阵列数据与对照病例进行了比较。确定了 64 个单核苷酸多态性 (SNP)，其中 IBD 的相关风险受吸烟影响。这些 SNP 中近一半与已知与 IBD 相关的 SNP 接近，并且许多位于与粘膜屏障调节和免疫反应相关的基因附近。20 个 SNP 位于 6p21 的人类白细胞抗原区域内，因此对适应性免疫的影响可能是对基因-吸烟相互作用的解释。在克罗恩病和 UC 中，七个 SNP 以相反的方向与吸烟相互作用。以前吸烟者、曾经吸烟者和现在吸烟者之间也存在对比。在通风的吸烟室中暴露于烟雾中的基因敲除小鼠模型中评估了两个被确定为可能与吸烟相互作用的基因，Il10 和 Nod2，相当于每天抽五支烟，持续 8 周。Il10 缺陷小鼠发展为加速结肠炎和回肠炎。Nod2 缺陷小鼠出现回肠炎。在暴露于烟雾的野生型小鼠中，没有 IBD 的迹象。因此，Il10 和 Nod2 对吸烟有保护作用，并且可能在疾病定位中起作用。总之，