The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants

Alcohol Res Health. 2007;30(1):5-13.

Abstract

The primary enzymes involved in alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both enzymes occur in several forms that are encoded by different genes; moreover, there are variants (i.e., alleles) of some of these genes that encode enzymes with different characteristics and which have different ethnic distributions. Which ADH or ALDH alleles a person carries influence his or her level of alcohol consumption and risk of alcoholism. Researchers to date primarily have studied coding variants in the ADH1 B, ADH1C, and ALDH2 genes that are associated with altered kinetic properties of the resulting enzymes. For example, certain ADH1B and ADH1C alleles encode particularly active ADH enzymes, resulting in more rapid conversion of alcohol (i.e., ethanol) to acetaldehyde; these alleles have a protective effect on the risk of alcoholism. A variant of the ALDH2 gene encodes an essentially inactive ALDH enzyme, resulting in acetaldehyde accumulation and a protective effect. It is becoming clear that noncoding variants in both ADH and ALDH genes also may influence alcohol metabolism and, consequently, alcoholism risk; the specific nature and effects of these variants still need further study.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alcohol Dehydrogenase / genetics
  • Alcohol Dehydrogenase / metabolism*
  • Alcoholism / enzymology*
  • Alcoholism / genetics*
  • Aldehyde Dehydrogenase / genetics*
  • Aldehyde Dehydrogenase / metabolism
  • Aldehyde Dehydrogenase 1 Family
  • Alleles
  • Ethanol / metabolism*
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Neurophysins / genetics
  • Protein Precursors / genetics
  • Retinal Dehydrogenase
  • Vasopressins / genetics

Substances

  • AVP protein, human
  • Neurophysins
  • Protein Precursors
  • Vasopressins
  • Ethanol
  • Alcohol Dehydrogenase
  • Aldehyde Dehydrogenase 1 Family
  • Aldehyde Dehydrogenase
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase