Investigation of the role of polymorphisms at the alcohol... : Hepatology (original) (raw)

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Day, Christopher P.1; Bashir, Rumaisa1; James, Oliver F. W.1; Bassendine, Margaret F. M.D.*, 1; Crabb, David W.2; Thomasson, Holly R.2; Li, Ting-Kai2; Edenberg, Howard J.2

1University of Newcastle Upon Tyne, Department of Medicine, The Medical School, Framlington Place, Newcastle Upon Tyne, NE2 4HH, United Kingdom

2Department of Medicine, Biochemistry and Molecular Biology and Medical Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202-5122

*Address reprint requests to: University of Newcastle Upon Tyne, Medical Molecular Biology Group, 4th floor, Catherine Cookson Bldg., NE2 4HH, UK.

Received December 27, 1990; Accepted June 07, 1991; previously published online December 08, 2005

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 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. _ADH_3 allele frequencies were different in patients and control subjects. _ADH_3★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.

Copyright © 1991 American Association for the Study of Liver Diseases.