Genetics of ethanol metabolism and alcoholic liver disease

Paul Kwo, David W. Crabb

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Scopus citations

Abstract

The metabolism of ethanol in part determines its pharmacological properties and toxicity. Ethanol metabolizing systems, including alcohol and aldehyde dehydrogenases and cytochrome P450 2E1, are genetically polymorphic. Inheritance of high activity ADH2*2 has been associated with decreased drinking and risk of alcoholism, and is probably associated with increased risk of liver damage with heavy drinking. Inheritance of the dominant negative ALDH2*2 allele markedly reduces alcohol consumption and risk of alcoholism, but also may predispose to increased hepatic toxicity of alcohol. ALDH2*2 is also associated with increased risk of esophageal and upper airway cancer. Thus, inheritance of enzyme variants which would be expected to lead to increased intrahepatic production of acetaldehyde (high activity ADH) or reduced disposal of acetaldehyde (inactive ALDH2) appear to correlate with aversion to drinking. Individuals who persist in heavy drinking despite the aversive reactions may be at increased risk of liver injury. Promoter variants of cytochrome P450 2E1 have been studied in many populations for association with alcoholic liver disease or alcoholism, but the results have been controversial. A number of other genetic variations have been reported in association with alcoholic liver disease, and these findings need to be confirmed.

Original languageEnglish (US)
Title of host publicationEthanol and the Liver
Subtitle of host publicationMechanisms and Management
PublisherCRC Press
Pages95-129
Number of pages35
ISBN (Electronic)9781420024272
ISBN (Print)9780415275828
StatePublished - Jan 1 2002

Keywords

  • Alcohol dehydrogenase
  • Alcoholism
  • Aldehyde dehydrogenase
  • Cytochrome P450
  • Enzyme
  • Ethanol
  • Genetics
  • Liver
  • Liver disease
  • Pharmacogenetics
  • Pharmacokinetics
  • Stomach

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Genetics of ethanol metabolism and alcoholic liver disease'. Together they form a unique fingerprint.

  • Cite this

    Kwo, P., & Crabb, D. W. (2002). Genetics of ethanol metabolism and alcoholic liver disease. In Ethanol and the Liver: Mechanisms and Management (pp. 95-129). CRC Press.