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).

从全基因组关联研究中鉴定与脂肪肝疾病 (FLD) 相关的遗传变异始于 2008 年，当时发现PNPLA3中的单核苷酸多态性与肝脂肪改变相关，PNPLA3 是编码 patatin 样磷脂酶结构域 3 的基因。内容。从那时起，已经确定了几种与预防 FLD 或增加 FLD 风险相关的基因变异。这些变异的识别使我们能够深入了解导致 FLD 的代谢途径，并能够识别潜在的治疗靶点。在这篇小型综述中，我们将研究来自 FLD 基因验证靶点的治疗机会，包括针对PNPLA3和HSD17 B 1 3 的基于寡核苷酸的疗法，目前正在临床试验中评估这些疗法用于治疗 NASH（非酒精性脂肪性肝炎） ）。