The genetics of alcohol dependence and alcohol-related liver disease

JOURNAL OF HEPATOLOGY

卷:66

Review

Stickel, Felix¹  Moreno, Christophe^2,3  Hampe, Jochen⁴  Morgans, Marsha Y.⁵ 

[1] Univ Zurich Hosp, Dept Gastroenterol & Hepatol, Ramistr 100, CH-8091 Zurich, Switzerland

[2] Univ Libre Bruxelles, Dept Gastroenterol Hepatopancreatol & Digest Onco, CUB Hop Erasme, Brussels, Belgium

[3] Univ Libre Bruxelles, Lab Expt Gastroenterol, Brussels, Belgium

[4] Tech Univ Dresden, Dept Med 1, Univ Hosp Dresden, Dresden, Germany

[5] UCL, UCL Inst Liver & Digest Hlth, Div Med, Royal Free Campus, London, England

关键词: Alcohol dependence;    Alcohol metabolism;    Alcohol use disorders;    Liver Cirrhosis;    Alcoholic;    Genome-wide association study;    Heritability;    estimates;    Phenotypic variability;    Substance-related disorders;    Alcohol dehydrogenase;    Alcoholism;    Aldehyde oxidoreductases;    Ethanol;   

DOI  :  10.1016/j.jhep.2016.08.011

来源: Elsevier

【 摘 要 】

The susceptibility to developing alcohol dependence and significant alcohol-related liver injury is determined by a number of constitutional, environmental and genetic factors, although the nature and level of interplay between them remains unclear. The familiality and heritability of alcohol dependence is well-documented but, to date, no strong candidate genes conferring increased risk have emerged, although variants in alcohol dehydrogenase and acetaldehyde dehydrogenase have been shown to confer protection, predominantly in individuals of East Asian ancestry. Population contamination with confounders such as drug co-dependence and psychiatric and physical co-morbidity may explain the essentially negative genome-wide association studies in this disorder. The familiality and hereditability of alcohol-related cirrhosis is not as well-documented but three strong candidate genes PNPLA3, TM6SF2 and MBOAT7, have been identified. The mechanisms by which variants in these genes confer risk and the nature of the functional interplay between them remains to be determined but, when elucidated, will undoubtedly increase our understanding of the pathophysiology of this disease. The way in which this genetic information could potentially inform patient management has yet to be determined and tested. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

Free