Hernaez Ruben
Department of Medicine, The Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
Gastroenterol Hepatol. 2012 Jan;35(1):32-41. doi: 10.1016/j.gastrohep.2011.08.002. Epub 2011 Nov 16.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Whereas insulin resistance and obesity are considered major risk factors for the development and progression of NAFLD, the genetic underpinnings are unclear. Before 2008, candidate gene studies based on prior knowledge of pathophysiology of fatty liver yielded conflicting results. In 2008, Romeo et al. published the first genome wide association study and reported the strongest genetic signal for the presence of fatty liver (PNPLA3, patatin-like phospholipase domain containing 3; rs738409). Since then, two additional genome wide scans were published and identified 9 additional genetic variants. Whereas these results shed light into the understanding of the genetics of NAFLD, most of associations have not been replicated in independent samples and, therefore, remain undetermined the significance of these findings. This review aims to summarize the understanding of genetic epidemiology of NAFLD and highlights the gaps in knowledge.
非酒精性脂肪性肝病（NAFLD）是全球最常见的慢性肝病。虽然胰岛素抵抗和肥胖被认为是NAFLD发生和进展的主要危险因素，但其遗传基础尚不清楚。2008年之前，基于对脂肪肝病理生理学的先验知识进行的候选基因研究得出了相互矛盾的结果。2008年，罗密欧等人发表了第一项全基因组关联研究，并报告了脂肪肝存在的最强遗传信号（PNPLA3，含帕他汀样磷脂酶结构域3；rs738409）。从那时起，又发表了另外两项全基因组扫描，并确定了另外9个遗传变异。虽然这些结果有助于理解NAFLD的遗传学，但大多数关联尚未在独立样本中得到重复验证，因此，这些发现的意义仍未确定。本综述旨在总结对NAFLD遗传流行病学的理解，并突出知识空白。
