Semin Liver Dis 2007; 27(1): 044-054
DOI: 10.1055/s-2006-960170
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Genetics of Alcoholic Liver Disease and Nonalcoholic Fatty Liver Disease

Nimantha Mark Wilfred de Alwis1 , 2 , Christopher Paul Day1 , 2
  • 1School of Clinical Medical Sciences, The Medical School, Newcastle upon Tyne, United Kingdom
  • 2Liver Research Group, Institute of Cellular Medicine, Newcastle University, United Kingdom
Further Information

Publication History

Publication Date:
12 February 2007 (online)


Although the vast majority of heavy drinkers and individuals with obesity, insulin resistance, and the metabolic syndrome have steatosis, only a minority ever develop steatohepatitis, fibrosis, and cirrhosis. Genetic and environmental risk factors for advanced alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) seem likely to include factors that influence the severity of steatosis and oxidative stress, the cytokine milieu, the magnitude of the immune response, and/or the severity of liver fibrosis. For ALD, the dose and pattern of alcohol intake, coffee intake, and dietary and other lifestyle factors leading to obesity are the most important environmental determinants of disease risk. For NAFLD, dietary saturated fat and antioxidant intake, small bowel bacterial overgrowth, and obstructive sleep apnea syndrome may play a role. Family studies and interethnic variations in susceptibility suggest that genetic factors are important in determining disease risk. For ALD, functional polymorphisms in the ADH and ALDH alcohol metabolizing genes play a role in determining susceptibility in Oriental populations. No genetic associations with advanced NAFLD have been replicated in large studies. Preliminary data suggest that polymorphisms in the genes encoding microsomal triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin receptor, tumor necrosis factor α, transforming growth factor β, and angiotensinogen may be associated with steatohepatitis or hepatic fibrosis or both.


Professor Christopher Paul Day, M.D. , F.R.C.P. , Ph.D. 

School of Clinical Medical Sciences, Floor 4 William Leech Building, The Medical School

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