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. 1983 Nov;35(6):1107–1116.

Determination of genotypes of human aldehyde dehydrogenase ALDH2 locus.

A Yoshida, G Wang, V Davé
PMCID: PMC1685980  PMID: 6650498

Abstract

Virtually all Caucasians have two major aldehyde dehydrogenase isozymes, ALDH1 and ALDH2, in their livers, while approximately 50% of Japanese and other Orientals are "atypical" in that they have only ALDH1 and are missing ALDH2. We previously demonstrated the existence of an enzymatically inactive but immunologically cross-reactive material (CRM) in atypical Japanese livers. Among 10 Japanese livers examined, five had ALDH1 but not ALDH2 isozyme. These are considered to be homozygous atypical at the ALDH2 locus. Four had both ALDH1 and ALDH2 components detected by starch gel electrophoresis, that is, they are apparently usual. However, biochemical and immunological studies revealed that three of these four livers contained CRM. These three livers should be heterozygous atypical in the ALDH2 locus, that is, genotype ALDH2(1)/ALDH2(2). A Japanese liver, as well as control Caucasian livers, had no CRM, and they must be homozygous usual ALDH2(1)/ALDH2(1). Although the number of liver specimens examined is limited, the frequencies of three genotypes determined in this study are compatible with the values calculated based on the genetic model that two common alleles ALDH2(1) and ALDH2(2) for the same locus are codominantly expressed in Orientals. The remaining liver had only ALDH2 isozyme and was missing ALDH1. This type was not previously found in Caucasians and Orientals. The two-dimensional crossed immunoelectrophoresis revealed the existence of a CRM corresponding to ALDH1 in this liver. The abnormality can be considered to be due to structural mutation at the ALDH1 locus producing a defective ALDH1 molecule, although other possibilities such as post-translational modifications are not ruled out.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Crow K. E., Kitson T. M., MacGibbon A. K., Batt R. D. Intracellular localisation and properties of aldehyde dehydrogenases from sheep liver. Biochim Biophys Acta. 1974 May 20;350(1):121–128. doi: 10.1016/0005-2744(74)90209-5. [DOI] [PubMed] [Google Scholar]
  2. Eckfeldt J. H., Yonetani T. Subcellular localization of the F1 and F2 isozymes of horse liver aldehyde dehydrogenase. Arch Biochem Biophys. 1976 Aug;175(2):717–722. doi: 10.1016/0003-9861(76)90564-6. [DOI] [PubMed] [Google Scholar]
  3. Eckfeldt J., Mope L., Takio K., Yonetani T. Horse liver aldehyde dehydrogenase. Purification and characterization of two isozymes. J Biol Chem. 1976 Jan 10;251(1):236–240. [PubMed] [Google Scholar]
  4. Goedde H. W., Agarwal D. P., Harada S. Genetic studies on alcohol-metabolizing enzymes: detection of isozymes in human hair roots. Enzyme. 1980;25(4):281–286. doi: 10.1159/000459265. [DOI] [PubMed] [Google Scholar]
  5. Goedde H. W., Harada S., Agarwal D. P. Racial differences in alcohol sensitivity: a new hypothesis. Hum Genet. 1979 Oct 2;51(3):331–334. doi: 10.1007/BF00283404. [DOI] [PubMed] [Google Scholar]
  6. Greenfield N. J., Pietruszko R. Two aldehyde dehydrogenases from human liver. Isolation via affinity chromatography and characterization of the isozymes. Biochim Biophys Acta. 1977 Jul 8;483(1):35–45. doi: 10.1016/0005-2744(77)90005-5. [DOI] [PubMed] [Google Scholar]
  7. Harada S., Misawa S., Agarwal D. P., Goedde H. W. Liver alcohol dehydrogenase and aldehyde dehydrogenase in the Japanese: isozyme variation and its possible role in alcohol intoxication. Am J Hum Genet. 1980 Jan;32(1):8–15. [PMC free article] [PubMed] [Google Scholar]
  8. Ikawa M., Impraim C. C., Wang G., Yoshida A. Isolation and characterization of aldehyde dehydrogenase isozymes from usual and atypical human livers. J Biol Chem. 1983 May 25;258(10):6282–6287. [PubMed] [Google Scholar]
  9. Impraim C., Wang G., Yoshida A. Structural mutation in a major human aldehyde dehydrogenase gene results in loss of enzyme activity. Am J Hum Genet. 1982 Nov;34(6):837–841. [PMC free article] [PubMed] [Google Scholar]
  10. Kitabatake N., Sasaki R., Chiba H. Localization of bovine liver aldehyde dehydrogenase isozymes and their immunological properties. J Biochem. 1981 Apr;89(4):1223–1229. [PubMed] [Google Scholar]
  11. LAURELL C. B. ANTIGEN-ANTIBODY CROSSED ELECTROPHORESIS. Anal Biochem. 1965 Feb;10:358–361. doi: 10.1016/0003-2697(65)90278-2. [DOI] [PubMed] [Google Scholar]
  12. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  13. Mizoi Y., Ijiri I., Tatsuno Y., Kijima T., Fujiwara S., Adachi J., Hishida S. Relationship between facial flushing and blood acetaldehyde levels after alcohol intake. Pharmacol Biochem Behav. 1979 Feb;10(2):303–311. doi: 10.1016/0091-3057(79)90105-9. [DOI] [PubMed] [Google Scholar]
  14. Stamatoyannopoulos G., Chen S. H., Fukui M. Liver alcohol dehydrogenase in Japanese: high population frequency of atypical form and its possible role in alcohol sensitivity. Am J Hum Genet. 1975 Nov;27(6):789–796. [PMC free article] [PubMed] [Google Scholar]
  15. Stowell A., Hillbom M., Salaspuro M., Lindros K. O. Low acetaldehyde levels in blood, breath and cerebrospinal fluid of intoxicated humans as assayed by improved methods. Adv Exp Med Biol. 1980;132:635–645. doi: 10.1007/978-1-4757-1419-7_66. [DOI] [PubMed] [Google Scholar]
  16. Teng Y. S. Human liver aldehyde dehydrogenase in Chinese and Asiatic Indians: gene deletion and its possible implications in alcohol metabolism. Biochem Genet. 1981 Feb;19(1-2):107–114. doi: 10.1007/BF00486141. [DOI] [PubMed] [Google Scholar]
  17. WASSERMAN E., LEVINE L. Quantitative micro-complement fixation and its use in the study of antigenic structure by specific antigen-antibody inhibition. J Immunol. 1961 Sep;87:290–295. [PubMed] [Google Scholar]
  18. Yoshida A. Differences in the isozymes involved in alcohol metabolism between caucasians and orientals. Isozymes Curr Top Biol Med Res. 1983;8:245–261. [PubMed] [Google Scholar]
  19. Yoshida A. Molecular basis of difference in alcohol metabolism between orientals and caucasians. Jinrui Idengaku Zasshi. 1982 Jun;27(2):55–70. doi: 10.1007/BF01993894. [DOI] [PubMed] [Google Scholar]

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