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

Christopher P. Day, Rumaisa Bashir, Oliver F W James, Margaret F. Bassendine, David Crabb, Holly R. Thomasson, Ting Kai Li, Howard Edenberg

Research output: Contribution to journalArticle

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Abstract

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 τ 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. All patients and all but one control subject were homozygous ADH2*1, encoding the β1 subunit. No ADH2*3 alleles were detected. All 34 patients and 39 control subjects tested were homozygous ALDH2*1 encoding the active enzyme. ADH3 allele frequencies were different in patients and control subjects. ADH3*1 frequency: control subjects, 55.1%; cirrhotic patients, 62.7%; chronic pancreatitis patients, 65.4%. The difference between the patient groups combined and the control subjects was significant (p < 0.05; G-test of Sokal and Rohlf) if it was assumed that the allele frequency in our control population was a reasonable estimate of our local population allele frequency. These results suggest that genetically determined differences in alcohol metabolism may, in part, explain predisposition to alcohol-related end-organ damage.

Original languageEnglish
Pages (from-to)798-801
Number of pages4
JournalHepatology
Volume14
Issue number5
StatePublished - Nov 1991

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Aldehyde Dehydrogenase
Alcohol Dehydrogenase
Genetic Predisposition to Disease
Alcohols
Gene Frequency
Alleles
Chronic Pancreatitis
Oligonucleotide Probes
DNA-Directed DNA Polymerase
Population
Alcoholism
Healthy Volunteers
Leukocytes
Fibrosis
Ethanol
Polymerase Chain Reaction
Control Groups
Enzymes

ASJC Scopus subject areas

  • Hepatology

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Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol-related end-organ damage. / Day, Christopher P.; Bashir, Rumaisa; James, Oliver F W; Bassendine, Margaret F.; Crabb, David; Thomasson, Holly R.; Li, Ting Kai; Edenberg, Howard.

In: Hepatology, Vol. 14, No. 5, 11.1991, p. 798-801.

Research output: Contribution to journalArticle

Day, Christopher P. ; Bashir, Rumaisa ; James, Oliver F W ; Bassendine, Margaret F. ; Crabb, David ; Thomasson, Holly R. ; Li, Ting Kai ; Edenberg, Howard. / Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol-related end-organ damage. In: Hepatology. 1991 ; Vol. 14, No. 5. pp. 798-801.
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AB - 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 τ 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. All patients and all but one control subject were homozygous ADH2*1, encoding the β1 subunit. No ADH2*3 alleles were detected. All 34 patients and 39 control subjects tested were homozygous ALDH2*1 encoding the active enzyme. ADH3 allele frequencies were different in patients and control subjects. ADH3*1 frequency: control subjects, 55.1%; cirrhotic patients, 62.7%; chronic pancreatitis patients, 65.4%. The difference between the patient groups combined and the control subjects was significant (p < 0.05; G-test of Sokal and Rohlf) if it was assumed that the allele frequency in our control population was a reasonable estimate of our local population allele frequency. These results suggest that genetically determined differences in alcohol metabolism may, in part, explain predisposition to alcohol-related end-organ damage.

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