Advertisement

A Polymorphism in the Rat Liver Mitochondrial ALDH2 Gene is Associated with Alcohol Drinking Behavior

  • L. Carr
  • B. Mellencamp
  • D. Crabb
  • L. Lumeng
  • T.-K. Li
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 284)

Abstract

Liver mitochondrial aldehyde dehydrogenase (ALDH2) has a low Km for acetaldehyde and plays a major role in acetaldehyde oxidation in vivo following alcohol consumption. In humans, a single base pair mutation produces a catalytically inactive enzyme (Yoshida et al., 1984). Approximately 50% of Asians have this defective ALDH2 allele; upon ingestion of ethanol, these individuals experience classic symptoms of acetaldehyde accumulation (Mizoi et al., 1979) which deters alcohol-drinking and thus reduces the risk of becoming an alcoholic. Japanese alcoholics have a low incidence of the ALDH2-deficient phenotype (2.3%) compared with the general Japanese population (41%) suggesting that polymorphism of ALDH2 could play a role in an individual’s susceptibility to alcoholism (Harada et al., 1982).

Keywords

Aldehyde Dehydrogenase ALDH2 Activity General Japanese Population ALDH2 Gene Acetaldehyde Accumulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Yoshida, A., Huang, I.-Y., and Ikawa, M., 1984, Molecular abnormality of an inactive aldehyde dehydrogenase gene results in loss of enzyme activity, Proc. Natl. Acad. Sci., 81:258–161, USA.PubMedCrossRefGoogle Scholar
  2. Mizoi, Y., Ijiri, I., Tatsuno, Y., Kijima, T., Fujiwara, S., Adachi, J., 1979, Relationship between facial flushing and blood acetaldehyde levels after alcohol intake, Pharmacol. Biochem. Behav., 10:303–311.PubMedCrossRefGoogle Scholar
  3. Harada, S., Agarwal, D. P., Goedde, H. W., and Ishikawa, B., 1983, Aldehyde dehydrogenase isoenzyme variation and alcoholism in Japan, Pharmacol. Biochem. Behav., 18 (Suppl. 1): 151–153.PubMedCrossRefGoogle Scholar
  4. Li, T.-K, Lumeng, L., McBride, W. J., Murphy, J. M., 1987, Rodent lines selected for factors affecting alcohol sumption, Alcohol and Alcoholism, Suppl. 1:91–97.Google Scholar
  5. Johnson, D., and Lardy, H. A., 1967, IN Methods in Enzymology (Estabrook, R. W., and Pullman, M. E., eds.), 10:94–96.CrossRefGoogle Scholar
  6. Rex, D. K., Bosron, W. F., Smialek, J. E., and Li, T.-K., 1985, Alcohol and aldehyde dehydrogenase isoenzymes in North American Indians, Alcohol. Clin. Exp. Res., 9:147–152.PubMedCrossRefGoogle Scholar
  7. Chomczynski, P., and Sacchi, N., 1987, Single-step method of RNA isolation of acid guanidinium thiocyanate-phenol-chloroform extraction, Anal. Biochem., 162:157–159.CrossRefGoogle Scholar
  8. Saiki, R. K., Scharf, S., Faloona, F., Mullis, K. B., Horn, G. T., Erlich, H. A., Arnheim, N., 1985, Enzymatic amplification of B-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia, Science, 230:1350–1354.PubMedCrossRefGoogle Scholar
  9. Farres, J., Guan, K.-L., Weiner, H., 1989, Primary structures of rat and bovine liver mitochondrial aldehyde dehydrogenases reduced from cDNA sequences, Eur. J. Biochem., 180:67–74.PubMedCrossRefGoogle Scholar
  10. Crabb, D. W., Edenberg, H. J., Bosron, W. F., Li, T.-K., 1989. Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity, J. Clin. Invest., 83:314–316.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • L. Carr
    • 1
  • B. Mellencamp
    • 1
  • D. Crabb
    • 1
  • L. Lumeng
    • 1
  • T.-K. Li
    • 1
  1. 1.Indiana University School of Medicine and VA Medical CenterIndianapolisUSA

Personalised recommendations