Salem Mohammad, Ammitzboell Mette, Nys Kris, Seidelin Jakob Benedict, Nielsen Ole Haagen
a Department of Gastroenterology ; Medical Section; Herlev Hospital; University of Copenhagen ; Copenhagen , Denmark.
Autophagy. 2015 Apr 3;11(4):585-94. doi: 10.1080/15548627.2015.1017187.
Genetic variations in the autophagic pathway influence genetic predispositions to Crohn disease. Autophagy, the major lysosomal pathway for degrading and recycling cytoplasmic material, constitutes an important homeostatic cellular process. Of interest, single-nucleotide polymorphisms in ATG16L1 (autophagy-related 16-like 1 [S. cerevisiae]), a key component in the autophagic response to invading pathogens, have been associated with an increased risk of developing Crohn disease. The most common and well-studied genetic variant of ATG16L1 (rs2241880; leading to a T300A conversion) exhibits a strong association with risk for developing Crohn disease. The rs2241880 variant plays a crucial role in pathogen clearance, resulting in imbalanced cytokine production, and is linked to other biological processes, such as the endoplasmic reticulum stress/unfolded protein response. In this review, we focus on the importance of ATG16L1 and its genetic variant (T300A) within the elementary biological processes linked to Crohn disease.
自噬途径中的基因变异会影响克罗恩病的遗传易感性。自噬是降解和循环利用细胞质物质的主要溶酶体途径，是细胞内重要的稳态维持过程。有趣的是，自噬相关16样蛋白1（酿酒酵母）（ATG16L1）中的单核苷酸多态性，作为对入侵病原体自噬反应的关键组成部分，与克罗恩病的发病风险增加有关。ATG16L1最常见且研究充分的基因变异（rs2241880；导致T300A转换）与克罗恩病的发病风险密切相关。rs2241880变异在病原体清除中起关键作用，导致细胞因子产生失衡，并与其他生物学过程相关，如内质网应激/未折叠蛋白反应。在本综述中，我们重点关注ATG16L1及其基因变异（T300A）在与克罗恩病相关的基本生物学过程中的重要性。
