慢性胰腺炎：遗传风险因素的最新进展。
Chronic pancreatitis: an update on genetic risk factors.
作者信息
Weiss Frank U, Skube Mariya E, Lerch Markus M
机构信息
Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
出版信息
Curr Opin Gastroenterol. 2018 Sep;34(5):322-329. doi: 10.1097/MOG.0000000000000461.
Abstract
PURPOSE OF REVIEW
Genetic mutations in genes within and outside of the trypsin-dependent pathologic pathway have been found to be associated with chronic pancreatitis. This review highlights recent developments.
RECENT FINDINGS
CTRB1-CTRB2 has been identified as a new risk locus for chronic pancreatitis and the disease mechanism may involve trypsin degradation. Misfolding mutations in PRSS1, CPA1, and CEL, as well as environmental stress factors like tobacco and alcohol can trigger endoplasmic reticulum stress (ER-Stress).
SUMMARY
Protein misfolding as well as enzyme activity changes due to altered autoactivation, intracellular degradation, or enzyme inhibition represent the most important pathological mechanisms of chronic pancreatitis to date. Analysis of composite risk patterns by next-generation sequencing will help elucidate complex gene interactions and identify new potential therapeutic targets.
摘要
综述目的
已发现胰蛋白酶依赖性病理途径内外基因的基因突变与慢性胰腺炎相关。本综述重点介绍了近期的进展。
最新发现
CTRB1-CTRB2已被确定为慢性胰腺炎的一个新风险位点，其发病机制可能涉及胰蛋白酶降解。PRSS1、CPA1和CEL中的错误折叠突变，以及烟草和酒精等环境应激因素可引发内质网应激（ER应激）。
总结
蛋白质错误折叠以及由于自激活改变、细胞内降解或酶抑制导致的酶活性变化是迄今为止慢性胰腺炎最重要的病理机制。通过下一代测序分析复合风险模式将有助于阐明复杂的基因相互作用并确定新的潜在治疗靶点。
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