Genetic determinants of pancreatitis: relevance in severe hypertriglyceridemia.

IF 3.8 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in lipidology Pub Date : 2023-04-01 DOI:10.1097/MOL.0000000000000866

Shyann M T Hang, Robert A Hegele, Amanda J Berberich

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引用次数: 1

Abstract

Purpose of review: Not all patients with severe hypertriglyceridemia develop acute pancreatitis. We surveyed recent literature on inter-individual genetic variation in susceptibility to pancreatitis.

Recent findings: Genetic determinants of pancreatitis include: rare Mendelian disorders caused by highly penetrant pathogenic variants in genes involved in trypsinogen activation; uncommon susceptibility variants in genes involved in trypsinogen activation, protein misfolding as well as calcium metabolism and cystic fibrosis, that have variable penetrance and show a range of odds ratios for pancreatitis; and common polymorphisms in many of the same genes that have only a small effect on risk. The role of these genetic variants in modulating pancreatitis risk in hypertriglyceridemia is unclear. However, among genetic determinants of plasma triglycerides, those predisposing to more severe hypertriglyceridemia associated with chylomicronemia appear to have higher pancreatitis risk.

Summary: Currently, among patients with severe hypertriglyceridemia, the most consistent predictor of pancreatitis risk is the triglyceride level. Furthermore, pancreatitis risk appears to be modulated by a higher genetic burden of factors associated with greater magnitude of triglyceride elevation. The role of common and rare genetic determinants of pancreatitis itself in this metabolic context is unclear.

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胰腺炎的遗传决定因素:与严重高甘油三酯血症相关。

回顾目的:并非所有严重高甘油三酯血症患者都会发展为急性胰腺炎。我们调查了最近关于胰腺炎易感性的个体间遗传变异的文献。最近发现:胰腺炎的遗传决定因素包括:由参与胰蛋白酶原激活的基因的高渗透致病性变异引起的罕见孟德尔疾病;参与胰蛋白酶原激活、蛋白质错误折叠、钙代谢和囊性纤维化的基因中不常见的易感性变异，它们在胰腺炎中具有可变的外显率和一系列的优势比;而许多相同基因的常见多态性对风险的影响很小。这些基因变异在调节高甘油三酯血症患者胰腺炎风险中的作用尚不清楚。然而，在血浆甘油三酯的遗传决定因素中，那些易患与乳糜微粒血症相关的更严重的高甘油三酯血症的人似乎有更高的胰腺炎风险。摘要:目前，在严重高甘油三酯血症患者中，最一致的胰腺炎风险预测指标是甘油三酯水平。此外，胰腺炎风险似乎受到与甘油三酯升高幅度较大相关因素的较高遗传负担的调节。在这种代谢背景下，常见和罕见的胰腺炎遗传决定因素本身的作用尚不清楚。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current opinion in lipidology 医学-内分泌学与代谢

CiteScore

6.70

自引率

4.50%

发文量

审稿时长

6-12 weeks

期刊介绍： With its easy-to-digest reviews on important advances in world literature, Current Opinion in Lipidology offers expert evaluation on a wide range of topics from six key disciplines including nutrition and metabolism, genetics and molecular biology, and hyperlipidaemia and cardiovascular disease. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by a section of Bimonthly Updates, which deliver an insight into new developments at the cutting edge of the disciplines covered in the journal.