Department of Medicine II (Gastroenterology and Endocrinology), Saarland University Medical Center, Saarland University, Homburg; Laboratory of Metabolic Liver Diseases, Center for Preclinical Research, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
Department of Medicine II (Gastroenterology and Endocrinology), Saarland University Medical Center, Saarland University, Homburg; Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany.
Gastroenterology. 2020 May;158(7):1865-1880.e1. doi: 10.1053/j.gastro.2020.01.053. Epub 2020 Feb 15.
Nonalcoholic fatty liver disease (NAFLD) is on the verge of becoming the leading cause of liver disease. NAFLD develops at the interface between environmental factors and inherited predisposition. Genome-wide association studies, followed by exome-wide analyses, led to identification of genetic risk variants (eg, PNPLA3, TM6SF2, and SERPINA1) and key pathways involved in fatty liver disease pathobiology. Functional studies improved our understanding of these genetic factors and the molecular mechanisms underlying the trajectories from fat accumulation to fibrosis, cirrhosis, and cancer over time. Here, we summarize key NAFLD risk genes and illustrate their interactions in a 3-dimensional "risk space." Although NAFLD genomics sometimes appears to be "lost in translation," we envision clinical utility in trial design, outcome prediction, and NAFLD surveillance.
非酒精性脂肪性肝病（NAFLD）即将成为肝脏疾病的主要病因。NAFLD 的发生是环境因素与遗传易感性相互作用的结果。全基因组关联研究，随后是外显子组分析，导致了遗传风险变异的鉴定（例如，PNPLA3、TM6SF2 和 SERPINA1）以及参与脂肪性肝病病理生物学的关键途径。功能研究提高了我们对这些遗传因素的理解，以及随着时间的推移从脂肪堆积到纤维化、肝硬化和癌症的分子机制。在这里，我们总结了关键的 NAFLD 风险基因，并在一个三维的“风险空间”中说明了它们的相互作用。尽管 NAFLD 基因组学有时似乎“难以转化为临床应用”，但我们设想在试验设计、结果预测和 NAFLD 监测方面具有临床应用价值。
