Abstract：
The identification of genetic variants associated with fatty liver disease (FLD) from genome-wide association studies started in 2008 when single nucleotide polymorphisms in PNPLA3, the gene encoding patatin-like phospholipase domain-containing 3, were found to be associated with altered hepatic fat content. Since then, several genetic variants associated with protection from, or an increased risk of, FLD have been identified. The identification of these variants has provided insight into the metabolic pathways that cause FLD and enabled the identification of potential therapeutic targets. In this mini-review, we will examine the therapeutic opportunities derived from genetically validated targets in FLD, including oligonucleotide-based therapies targeting PNPLA3 and HSD17B13 that are currently being evaluated in clinical trials for the treatment of NASH (non-alcoholic steatohepatitis).
摘要：
来自全基因组关联研究（GWAS）的与脂肪肝疾病（FLD）相关的遗传变异的鉴定始于2008年，当时发现PNPLA3中的单核苷酸多态性（编码含patatin样磷脂酶结构域的基因3）与肝脂肪含量改变有关。从那以后,已鉴定出几种与FLD保护或FLD风险增加相关的遗传变异.这些变体的鉴定允许深入了解引起FLD的代谢途径并鉴定治疗该疾病的治疗靶标。在这个小型审查中，我们将研究来自FLD基因验证靶标的治疗机会，包括PNPLA3和HSD17β13，目前正在非酒精性脂肪性肝炎（NASH）的临床试验中评估基于寡核苷酸的疗法。
