PNPLA3 expression and its impact on the liver: current perspectives.
PNPLA3 expression and its impact on the liver: current perspectives.
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DOI：
10.2147/hmer.s125718
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Trauner M
中科院分区：
文献类型：
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作者：
Bruschi FV;Tardelli M;Claudel T;Trauner M
人类PNPLA3类磷脂酶结构域3基因（PNPLA3）序列中出现的一种单核苷酸多态性，被称为I148M变异，是几种临床情况下最具特征和深入研究的变异之一，因为它与肝脂肪变性和更严重的疾病谱系（如非酒精性脂肪性肝炎、晚期纤维化和肝硬化）的风险增加密切相关。此外，I148M变异与酒精性肝病、慢性丙型肝炎相关肝硬化和肝细胞癌呈正相关。天然基因编码一种蛋白质，这种蛋白质在肝脏脂质代谢中的作用尚未完全确定，根据最近的观察，它似乎在不同的肝细胞类型（如肝星状细胞）中受到不同的调节。因此，本文旨在收集有关PNPLA3在人肝脏中表达的最新数据，并分析其遗传变异在人肝脏病理中的影响。此外，总结了动物模型和体外研究中与PNPLA3功能相关的当前生化和代谢数据，以便更好地理解该酶在肝脏疾病进展中的相关病理生理作用。
A single-nucleotide polymorphism occurring in the sequence of the human patatin-like phospholipase domain-containing 3 gene (PNPLA3), known as I148M variant, is one of the best characterized and deeply investigated variants in several clinical scenarios, because of its tight correlation with increased risk for developing hepatic steatosis and more aggressive part of the disease spectrum, such as nonalcoholic steatohepatitis, advanced fibrosis and cirrhosis. Further, the I148M variant is positively associated with alcoholic liver diseases, chronic hepatitis C–related cirrhosis and hepatocellular carcinoma. The native gene encodes for a protein that has not yet a fully defined role in liver lipid metabolism and, according to recent observations, seems to be divergently regulated among distinct liver cells type, such as hepatic stellate cells. Therefore, the aim of this review is to collect the latest data regarding PNPLA3 expression in human liver and to analyze the impact of its genetic variant in human hepatic pathologies. Moreover, a description of the current biochemical and metabolic data pertaining to PNPLA3 function in both animal models and in vitro studies is summarized to allow a better understanding of the relevant pathophysiological role of this enzyme in the progression of hepatic diseases.