1Bioscience Metabolism, Research and Early Development Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; Division of Endocrinology, Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: firstname.lastname@example.org.
2Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden; Clinical Nutrition Unit, Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy. Electronic address: email@example.com.
The identification of genetic variants associated with fatty liver disease (FLD) from genome wide association studies (GWASs) 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 increased risk of FLD have been identified. The identification of these variants has allowed insight into the metabolic pathways causing FLD and to identify therapeutic targets to treat the disease. In this mini-review we will examine the therapeutic opportunities derived from genetically validated targets in FLD, including PNPLA3 and HSD17β13, where oligonucleotide-based therapies are currently being evaluated in clinical trials for the treatment of non-alcoholic steatohepatitis (NASH).