Severson Tyler J, Besur Siddesh, Bonkovsky Herbert L
Tyler J Severson, Herbert L Bonkovsky, Department of Gastroenterology and Hepatology, Wake Forest University NC Baptist Medical Center, Winston-Salem, NC 27157, United States.
World J Gastroenterol. 2016 Aug 7;22(29):6742-56. doi: 10.3748/wjg.v22.i29.6742.
To investigate roles of genetic polymorphisms in non-alcoholic fatty liver disease (NAFLD) onset, severity, and outcome through systematic literature review.
The authors conducted both systematic and specific searches of PubMed through December 2015 with special emphasis on more recent data (from 2012 onward) while still drawing from more historical data for background. We identified several specific genetic polymorphisms that have been most researched and, at this time, appear to have the greatest clinical significance on NAFLD and similar hepatic diseases. These were further investigated to assess their specific effects on disease onset and progression and the mechanisms by which these effects occur.
We focus particularly on genetic polymorphisms of the following genes: PNPLA3, particularly the p. I148M variant, TM6SF2, particularly the p. E167K variant, and on variants in FTO, LIPA, IFNλ4, and iron metabolism, specifically focusing on HFE, and HMOX-1. We discuss the effect of these genetic variations and their resultant protein variants on the onset of fatty liver disease and its severity, including the effect on likelihood of progression to cirrhosis and hepatocellular carcinoma. While our principal focus is on NAFLD, we also discuss briefly effects of some of the variants on development and severity of other hepatic diseases, including hepatitis C and alcoholic liver disease. These results are briefly discussed in terms of clinical application and future potential for personalized medicine.
Polymorphisms and genetic factors of several genes contribute to NAFLD and its end results. These genes hold keys to future improvements in diagnosis and management.
通过系统的文献综述，研究基因多态性在非酒精性脂肪性肝病（NAFLD）发病、严重程度及预后中的作用。
作者对截至2015年12月的PubMed进行了系统和特定检索，特别强调了最新数据（2012年起），同时也参考了更多历史数据作为背景。我们确定了几个研究最多且目前似乎对NAFLD及类似肝病具有最大临床意义的特定基因多态性。对这些多态性进行了进一步研究，以评估它们对疾病发病和进展的具体影响以及这些影响发生的机制。
我们特别关注以下基因的多态性：PNPLA3，尤其是p.I148M变体；TM6SF2，尤其是p.E167K变体；以及FTO、LIPA、IFNλ4的变体和铁代谢相关基因，特别关注HFE和HMOX - 1。我们讨论了这些基因变异及其产生的蛋白质变体对脂肪肝疾病发病及其严重程度的影响，包括对进展为肝硬化和肝细胞癌可能性的影响。虽然我们主要关注NAFLD，但我们也简要讨论了一些变体对其他肝病，包括丙型肝炎和酒精性肝病的发生和严重程度的影响。从临床应用和个性化医疗的未来潜力方面简要讨论了这些结果。
几个基因的多态性和遗传因素促成了NAFLD及其最终结果。这些基因是未来改善诊断和管理的关键。
