Therapeutic opportunities for the treatment of NASH with genetically validated targets
- PMID: 37207913
- DOI: 10.1016/j.jhep.2023.05.007
Therapeutic opportunities for the treatment of NASH with genetically validated targets
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).
Keywords: CIDEB; Drug development; FLD; GPAM; GPAT1; HSD17B13; MAFLD; MARC1; MASLD; MBOAT7; MTARC1; NAFLD; NASH; PNPLA3; PSD3; SLD guidelines; adiponutrin; precision medicine; steatotic liver disease.
Copyright © 2023. Published by Elsevier B.V.
Similar articles
-
MTARC1 and HSD17B13 Variants Have Protective Effects on Non-Alcoholic Fatty Liver Disease in Patients Undergoing Bariatric Surgery.Int J Mol Sci. 2022 Dec 13;23(24):15825. doi: 10.3390/ijms232415825. Int J Mol Sci. 2022. PMID: 36555467 Free PMC article.
-
Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically characterised cohort☆.J Hepatol. 2020 Sep;73(3):505-515. doi: 10.1016/j.jhep.2020.04.003. Epub 2020 Apr 13. J Hepatol. 2020. PMID: 32298765
-
Review article: the emerging role of genetics in precision medicine for patients with non-alcoholic steatohepatitis.Aliment Pharmacol Ther. 2020 Jun;51(12):1305-1320. doi: 10.1111/apt.15738. Epub 2020 May 7. Aliment Pharmacol Ther. 2020. PMID: 32383295 Free PMC article. Review.
-
Genetic predisposition similarities between NASH and ASH: Identification of new therapeutic targets.JHEP Rep. 2021 Mar 30;3(3):100284. doi: 10.1016/j.jhepr.2021.100284. eCollection 2021 Jun. JHEP Rep. 2021. PMID: 34027340 Free PMC article. Review.
-
Insights into genetic variants associated with NASH-fibrosis from metabolite profiling.Hum Mol Genet. 2020 Dec 18;29(20):3451-3463. doi: 10.1093/hmg/ddaa162. Hum Mol Genet. 2020. PMID: 32720691 Free PMC article.
Cited by
-
Rab2A-mediated Golgi-lipid droplet interactions support very-low-density lipoprotein secretion in hepatocytes.EMBO J. 2024 Dec;43(24):6383-6409. doi: 10.1038/s44318-024-00288-x. Epub 2024 Nov 4. EMBO J. 2024. PMID: 39496977 Free PMC article.
-
GSDME promotes MASLD by regulating pyroptosis, Drp1 citrullination-dependent mitochondrial dynamic, and energy balance in intestine and liver.Cell Death Differ. 2024 Nov;31(11):1467-1486. doi: 10.1038/s41418-024-01343-0. Epub 2024 Jul 16. Cell Death Differ. 2024. PMID: 39009654
-
Systematic Review and Meta-Analysis: Prevalence of Non-Alcoholic Fatty Liver Disease and Liver Fibrosis in Patients with Inflammatory Bowel Disease.Nutrients. 2023 Oct 24;15(21):4507. doi: 10.3390/nu15214507. Nutrients. 2023. PMID: 37960160 Free PMC article. Review.
-
Current Status of Genetics and Polygenic Risk Scores in Metabolic Dysfunction-Associated Steatohepatitis.Gastroenterol Hepatol (N Y). 2024 Aug;20(8):460-503. Gastroenterol Hepatol (N Y). 2024. PMID: 39205952 Free PMC article. No abstract available.
-
Therapeutic management of metabolic dysfunction associated steatotic liver disease.United European Gastroenterol J. 2024 Mar;12(2):177-186. doi: 10.1002/ueg2.12525. Epub 2024 Jan 9. United European Gastroenterol J. 2024. PMID: 38193865 Free PMC article. Review.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous
