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通过全基因组关联研究揭示非酒精性脂肪性肝病的发病机制。

Unraveling the pathogenesis of non-alcoholic fatty liver diseases through genome-wide association studies.

机构信息

Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

Division of Nutritional Sciences, College of Agricultural, Consumer and Environmental Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.

出版信息

J Gastroenterol Hepatol. 2023 Nov;38(11):1877-1885. doi: 10.1111/jgh.16330. Epub 2023 Aug 17.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a significant health burden around the world, affecting approximately 25% of the population. Recent advances in human genetic databases have allowed for the identification of various single nucleotide polymorphisms associated with NAFLD-related traits. Investigating the functions of these genetic factors provides insight into the pathogenesis of NAFLD and potentially identifies novel therapeutic targets for NAFLD. In this review, we summarized current research on genes with NAFLD-associated mutations, highlighting phospholipid remodeling and spatially clustered loci as common pathological and genetic features of these mutations. These features suggest a complex yet intriguing mechanism of dissociated steatosis and insulin resistance, which is observed in a subset of patients and may lead to more precise therapy against NAFLD in the future.

摘要

非酒精性脂肪性肝病 (NAFLD) 是全球范围内的一个重大健康负担,影响约 25%的人口。人类遗传数据库的最新进展使得能够鉴定与 NAFLD 相关特征相关的各种单核苷酸多态性。研究这些遗传因素的功能可以深入了解 NAFLD 的发病机制,并为 NAFLD 潜在地确定新的治疗靶点。在这篇综述中,我们总结了与 NAFLD 相关突变的基因的当前研究,突出了磷脂重塑和空间聚集的基因座作为这些突变的常见病理和遗传特征。这些特征表明,在一部分患者中观察到的分离性脂肪变性和胰岛素抵抗存在复杂但有趣的机制,这可能为未来针对 NAFLD 的更精确治疗提供依据。

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