Genetic and Epigenetic Modifiers of Alcoholic Liver Disease

• Published in: International journal of molecular sciences Vol. 19; no. 12; p. 3857
• Main Authors: Meroni, Marica, Longo, Miriam, Rametta, Raffaela, Dongiovanni, Paola
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03-12-2018; MDPI
• Subjects: Age groups; alcoholic liver disease; Alcoholism; Cirrhosis; Dehydrogenases; Disease Progression; Enzymes; Epidemiology; Epigenesis, Genetic; Epigenetics; Estrogens; Ethanol; Ethnicity; Fatty acids; Fatty liver; Fibrosis; Genes, Modifier; Genetic diversity; Genetic Predisposition to Disease; Genetic variability; Genome-wide association studies; Genomes; Hepatocellular carcinoma; Humans; Inflammation; intestinal permeability; Lipid peroxidation; Liver; Liver cirrhosis; Liver diseases; Liver Diseases, Alcoholic - genetics; Liver Diseases, Alcoholic - pathology; MBOAT7; Metabolism; microRNAs; miRNA; Older people; Oxidation; Oxidative stress; Pathogenesis; PNPLA3; Public health; Review; Risk Factors; Steatosis; tight junctions; TM6SF2; Womens health; microRNAs; alcoholic liver disease; intestinal permeability; MBOAT7; PNPLA3; tight junctions; epigenetics; TM6SF2
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19123857

Alcoholic liver disease (ALD), a disorder caused by excessive alcohol consumption is a global health issue. More than two billion people consume alcohol in the world and about 75 million are classified as having alcohol disorders. ALD embraces a wide spectrum of hepatic lesions including steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). ALD is a complex disease where environmental, genetic, and epigenetic factors contribute to its pathogenesis and progression. The severity of alcohol-induced liver disease depends on the amount, method of usage and duration of alcohol consumption as well as on age, gender, presence of obesity, and genetic susceptibility. Genome-wide association studies and candidate gene studies have identified genetic modifiers of ALD that can be exploited as non-invasive biomarkers, but which do not completely explain the phenotypic variability. Indeed, ALD development and progression is also modulated by epigenetic factors. The premise of this review is to discuss the role of genetic variants and epigenetic modifications, with particular attention being paid to microRNAs, as pathogenic markers, risk predictors, and therapeutic targets in ALD.