Institute of Cellular Medicine, Newcastle University Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Expert Rev Gastroenterol Hepatol. 2011 Apr;5(2):253-63. doi: 10.1586/egh.11.18.
Nonalcoholic fatty liver disease (NAFLD) in most patients involves only simple hepatic steatosis; however, a minority develop progressive steatohepatitis. Family studies and inter-ethnic differences in susceptibility suggest that genetic factors may be important risk determinants for progressive disease. Polymorphisms in genes affecting lipid metabolism, cytokines, fibrotic mediators and oxidative stress may be associated with steatohepatitis and/or fibrosis, but most of these findings require replication. A recent finding that a nonsynonymous polymorphism in the PNPLA3 gene predicts the extent of steatosis in NAFLD has been replicated in at least eight studies, with several studies also demonstrating an association with fibrosis. A new genome-wide association study has identified several additional novel associations with NAFLD severity. Other disease genes may be identified by similar approaches in the future.
非酒精性脂肪性肝病（NAFLD）在大多数患者中仅涉及单纯性肝脂肪变性；然而，少数患者会发展为进行性脂肪性肝炎。家族研究和不同种族间的易感性差异表明，遗传因素可能是进行性疾病的重要危险因素。影响脂质代谢、细胞因子、纤维形成介质和氧化应激的基因多态性可能与脂肪性肝炎和/或纤维化有关，但这些发现大多需要重复。最近的一项研究发现，PNPLA3 基因的非同义多态性可预测 NAFLD 患者的脂肪变性程度，该发现已在至少八项研究中得到验证，其中几项研究还表明该多态性与纤维化有关。一项新的全基因组关联研究确定了与 NAFLD 严重程度相关的其他一些新的关联。未来可能会通过类似的方法发现其他疾病基因。
