Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol-related end-organ damage
Article first published online: 8 DEC 2005
Copyright © 1991 American Association for the Study of Liver Diseases
Volume 14, Issue 5, pages 798–801, November 1991
How to Cite
Day, C. P., Bashir, R., James, O. F. W., Bassendine, M. F., Crabb, D. W., Thomasson, H. R., Li, T.-K. and Edenberg, H. J. (1991), Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol-related end-organ damage. Hepatology, 14: 798–801. doi: 10.1002/hep.1840140509
- Issue published online: 8 DEC 2005
- Article first published online: 8 DEC 2005
- Manuscript Accepted: 7 JUN 1991
- Manuscript Received: 27 DEC 1990
- Newcastle Health Authority Research Committee
- National Institute of Alcoholism and Alcohol Abuse. Grant Numbers: DWC 0634, TKL AA 02343, AA 07611, HJE AA 06460
- Alcoholic Beverages Medical Research Foundation
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.
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.