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

Authors

  • Christopher P. Day,

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

    1. University of Newcastle Upon Tyne, Department of Medicine, The Medical School, Framlington Place, Newcastle Upon Tyne, NE2 4HH, United Kingdom
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  • Oliver F. W. James,

    1. University of Newcastle Upon Tyne, Department of Medicine, The Medical School, Framlington Place, Newcastle Upon Tyne, NE2 4HH, United Kingdom
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  • Margaret F. Bassendine M.D.,

    Corresponding author
    1. University of Newcastle Upon Tyne, Department of Medicine, The Medical School, Framlington Place, Newcastle Upon Tyne, NE2 4HH, United Kingdom
    • University of Newcastle Upon Tyne, Medical Molecular Biology Group, 4th floor, Catherine Cookson Bldg., NE2 4HH, UK
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  • David W. Crabb,

    1. Department of Medicine, Biochemistry and Molecular Biology and Medical Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202-5122
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  • Holly R. Thomasson,

    1. Department of Medicine, Biochemistry and Molecular Biology and Medical Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202-5122
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  • Ting-Kai Li,

    1. Department of Medicine, Biochemistry and Molecular Biology and Medical Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202-5122
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  • Howard J. Edenberg

    1. Department of Medicine, Biochemistry and Molecular Biology and Medical Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202-5122
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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 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 ADH21, encoding the β1 subunit. No ADH23 alleles were detected. All 34 patients and 39 control subjects tested were homozygous ALDH21 encoding the active enzyme. ADH3 allele frequencies were different in patients and control subjects. ADH31 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.

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