The genetics of alcoholic liver disease
Journal Title: Αρχεία Ελληνικής Ιατρικής - Year 2012, Vol 29, Issue 4
Abstract
Ethanol abuse is a major social and clinical problem. A proportion of chronic drinkers develop alcoholic liver disease (ALD), the incidence and severity of which is correlated with certain environmental factors and in particular with the quantity of alcohol consumed. In addition to direct damage to the liver, through steatosis, caused by excessive alcohol consumption, many other factors are considered to contribute to the pathogenesis and evolution of ALD and to the individual susceptibility to alcohol. Oxidative stress, generation of radical oxygen species (ROS), and secretion of cytokines, mainly of tumor necrosis factor α (TNF-α), are factors that lead to inflammation, fibrosis and ultimately cirrhosis of the liver. Current molecular biology methodology enables the isolation of genes and has contributed to the understanding of the structure and the relationships of genes involved in the pathogenesis of ALD. There is convincing documentation of the involvement of specific genes in the development of steatohepatitis, oxidative stress, the endotoxic response of Toll-like receptor-4 (TLR-4) and the activity of cytokines. It is known that chronic ethanol exposure leads to continuous endotoxin mediated TLR-4 and glycolsyl-phosphatidylinositol-anchored (CD14) gene activation and subsequent cytokine release, resulting in chronic inflammation and hepatocellular damage. Other genes have been identified which affect the evolution of early damage to fibrosis-cirrhosis and to the development of hepatocellular carcinoma. Better understanding of the pathophysiological mechanisms of ALD may lead to the formulation of novel effective forms of treatment in the future. This review presents developments in the manifestation of gene polymorphisms which regulate the pathogenesis and the natural history of ALD.
Authors and Affiliations
V. NEZI, L. VASILIEVA, M. DEUTSCH, S. DOURAKIS
Keywords
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Οικογενής μεσογειακός πυρετός. Μοριακή ανάλυση<br />