Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol‐related end‐organ damage

Little is known about factors determining individual susceptibility to the physical complications of alcohol abuse but genetically determined differences in ethanol metabolism may be important. The oxidative metabolism of alcohol is catalyzed by alcohol and aldehyde dehydrogenase. Polymorphisms have been observed at two of the five loci encoding alcohol dehydrogenase subunits: ADH2 (producing three β subunits) and ADH3 (producing two subunits) and also at the locus encoding the metabolically important form of aldehyde dehydrogenase, ALDH2. We have compared ADH2, ADH3 and ALDH2 allele frequencies in patients with alcohol‐related cirrhosis (n = 59) and chronic pancreatitis (n = 13) with 79 local healthy control subjects. The different alleles were detected with allele‐specific oligonucleotide probes after amplification of leukocyte DNA by the polymerase chain reaction.

[1]  Ting-kai Li,et al.  Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism , 1986, Hepatology.

[2]  Ting-kai Li,et al.  The human β3 alcohol dehydrogenase subunit differs from β1 by a cys for Arg-369 substitution which decreases NAD(H) binding , 1987 .

[3]  D. Tuma,et al.  Hypothesis: alcoholic liver injury and the covalent binding of acetaldehyde. , 1985, Alcoholism, clinical and experimental research.

[4]  H. Harris,et al.  Alcohol dehydrogenase isozymes in adult human stomach and liver: evidence for activity of the ADH3 locus , 1972, Annals of human genetics.

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

[6]  M. Smith,et al.  Genetics of human alcohol and aldehyde dehydrogenases. , 1986, Advances in human genetics.

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

[8]  A. Yoshida,et al.  Genotypes of alcohol-metabolizing enzymes in Japanese with alcohol liver diseases: a strong association of the usual Caucasian-type aldehyde dehydrogenase gene (ALDH1(2)) with the disease. , 1988, American journal of human genetics.

[9]  Ting-kai Li,et al.  Genotyping of human alcohol dehydrogenases at the ADH2 and ADH3 loci following DNA sequence amplification. , 1988, Genomics.

[10]  D. Agarwal,et al.  Polymorphism of aldehyde dehydrogenase and alcohol sensitivity. , 1987, Enzyme.

[11]  H. Edenberg,et al.  The human beta 3 alcohol dehydrogenase subunit differs from beta 1 by a Cys for Arg-369 substitution which decreases NAD(H) binding. , 1987, Biochemical and biophysical research communications.

[12]  W. K. Lelbach,et al.  CIRRHOSIS IN THE ALCOHOLIC AND ITS RELATION TO THE VOLUME OF ALCOHOL ABUSE , 1975, Annals of the New York Academy of Sciences.

[13]  D. Agarwal,et al.  Electrophoretic and biochemical studies of human aldehyde dehydrogenase isozymes in various tissues. , 1980, Life sciences.

[14]  N. Peterslund,et al.  Acvclovir in herpes zoster. , 1981 .

[15]  W. Bosron,et al.  Catalytic properties of human liver alcohol dehydrogenase isoenzymes. , 1987, Enzyme.

[16]  Bourdillon Jf.  A PLAN FOR TANGANYIKA. , 1964 .

[17]  G. Omenn,et al.  Evidence of genetic predisposition to alcoholic cirrhosis and psychosis: twin concordances for alcoholism and its biological end points by zygosity among male veterans. , 1981, Alcoholism, clinical and experimental research.

[18]  P. Gartside,et al.  Longevity among ethnic groups in alcoholic liver disease. , 1989, Alcohol and alcoholism.

[19]  J. Scott,et al.  VARIATION OF APOLIPOPROTEIN-B GENE IS ASSOCIATED WITH OBESITY, HIGH BLOOD CHOLESTEROL LEVELS, AND INCREASED RISK OF CORONARY HEART DISEASE , 1988, The Lancet.

[20]  I. P. Wartburg,et al.  ATYPICAL HUMAN LIVER ALCOHOL DEHYDROGENASE , 1968, Annals of the New York Academy of Sciences.

[21]  Ting-kai Li,et al.  Alcohol and aldehyde dehydrogenase genotypes and alcoholism in Chinese men. , 1991, American journal of human genetics.

[22]  L. Tsui,et al.  Report of the committee on the genetic constitution of chromosomes 7 and 8. , 1988, Cytogenetics and cell genetics.

[23]  H J Edenberg,et al.  Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. , 1989, The Journal of clinical investigation.

[24]  F. Rothhammer,et al.  Aldehyde dehydrogenase polymorphism in North American, South American, and Mexican Indian populations. , 1986, American journal of human genetics.

[25]  I. Ijiri,et al.  Alcohol sensitivity related to polymorphism of alcohol-metabolizing enzymes in Japanese , 1983, Pharmacology Biochemistry and Behavior.

[26]  A. Dilella,et al.  Hybridization of genomic DNA to oligonucleotide probes in the presence of tetramethylammonium chloride. , 1987, Methods in enzymology.

[27]  M. Omata,et al.  [ADH 2, 3 and ALDH 2 gene frequency in Japanese alcoholics]. , 1993, Nihon rinsho. Japanese journal of clinical medicine.

[28]  C. Lieber.  Biochemical and molecular basis of alcohol-induced injury to liver and other tissues. , 1988, The New England journal of medicine.

[29]  ThorkildI. A. Sørensen,et al.  PROSPECTIVE EVALUATION OF ALCOHOL ABUSE AND ALCOHOLIC LIVER INJURY IN MEN AS PREDICTORS OF DEVELOPMENT OF CIRRHOSIS , 1984, The Lancet.

[30]  Ting-kai Li,et al.  Genetic polymorphism of enzymes of alcohol metabolism and susceptibility to alcoholic liver disease. , 1988, Molecular aspects of medicine.