Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant.

Many Orientals lack the mitochondrial aldehyde dehydrogenase (ALDH2) activity responsible for the oxidation of acetaldehyde produced during ethanol metabolism. These individuals suffer the alcohol-flush reaction when they drink alcoholic beverages. The alcohol-flush reaction is the result of excessive acetaldehyde accumulation, and the unpleasant symptoms tend to reduce alcohol consumption. The subunit of this homotetrameric enzyme was sequenced and the abnormality in the inactive enzyme shown to be a substitution of lysine for glutamate at position 487. We have used the polymerase chain reaction to determine the genotypes of 24 livers from Japanese individuals. Correlating genotype with phenotype leads to the conclusion that the allele (ALDH2(2)) encoding the abnormal subunit is dominant.

[1]  D. Agarwal,et al.  Aldehyde Dehydrogenase Deficiency as Cause of Facial Flushing Reaction to Alcohol in Japanese , 1995, Alcohol health and research world.

[2]  T. Mohandas,et al.  Chromosomal assignment of the genes for human aldehyde dehydrogenase-1 and aldehyde dehydrogenase-2. , 1986, American journal of human genetics.

[3]  D. Agarwal,et al.  Population genetic and family studies on aldehyde dehydrogenase deficiency and alcohol sensitivity. , 1985, Alcohol.

[4]  R. Pietruszko,et al.  Human aldehyde dehydrogenase: catalytic activity in oriental liver. , 1984, Biochemical and biophysical research communications.

[5]  W. Bosron,et al.  Purification of human liver aldehyde dehydrogenase by high-performance liquid chromatography and identification of isoenzymes by immunoblotting. , 1987, Alcoholism, clinical and experimental research.

[6]  A. Yoshida,et al.  Structural mutation in a major human aldehyde dehydrogenase gene results in loss of enzyme activity. , 1982, American journal of human genetics.

[7]  C. Robert Cloninger,et al.  Inheritance of alcohol abuse. Cross-fostering analysis of adopted men. , 1981, Archives of general psychiatry.

[8]  K. Mullis,et al.  Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. , 1985, Science.

[9]  C. Robert Cloninger,et al.  Neurogenetic adaptive mechanisms in alcoholism. , 1987, Science.

[10]  A Yoshida,et al.  Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[11]  A. Yoshida,et al.  Determination of genotypes of human aldehyde dehydrogenase ALDH2 locus. , 1983, American journal of human genetics.

[12]  F. Ahern,et al.  Familial resemblances in flushing following alcohol use , 1982, Behavior genetics.

[13]  M. Bohman.  Some genetic aspects of alcoholism and criminality. A population of adoptees. , 1978, Archives of general psychiatry.

[14]  Agarwal Dp,et al.  Polymorphism of aldehyde dehydrogenase and alcohol sensitivity. , 1987 .

[15]  D. Agarwal,et al.  Genetic studies on alcohol-metabolizing enzymes: detection of isozymes in human hair roots. , 1980, Enzyme.

[16]  T. Kamada,et al.  Low Km ALDH isozyme and alcoholic liver injury , 1983, Pharmacology Biochemistry and Behavior.

[17]  D. Agarwal,et al.  Aldehyde dehydrogenase polymorphism and alcohol metabolism in alcoholics. , 1985, Alcohol.

[18]  A. Yoshida,et al.  Direct detection of usual and atypical alleles on the human aldehyde dehydrogenase-2 (ALDH2) locus. , 1987, American journal of human genetics.

[19]  I. Ijiri,et al.  Relationship between facial flushing and blood acetaldehyde levels after alcohol intake , 1979, Pharmacology Biochemistry and Behavior.

[20]  A. Yoshida,et al.  Isolation and characterization of aldehyde dehydrogenase isozymes from usual and atypical human livers. , 1983, The Journal of biological chemistry.

[21]  H. Jörnvall,et al.  Mitochondrial aldehyde dehydrogenase from human liver. Primary structure, differences in relation to the cytosolic enzyme, and functional correlations. , 1985, European journal of biochemistry.

[22]  D. Rex,et al.  Alcohol and aldehyde dehydrogenase isoenzymes in North American Indians. , 1985, Alcoholism, clinical and experimental research.

[23]  D. Agarwal,et al.  POSSIBLE PROTECTIVE ROLE AGAINST ALCOHOLISM FOR ALDEHYDE DEHYDROGENASE ISOZYME DEFICIENCY IN JAPAN , 1982, The Lancet.

[24]  A. Yoshida,et al.  Genomic structure of the human mitochondrial aldehyde dehydrogenase gene. , 1988, Genomics.