Gastrointestinal symptoms and ethanol metabolism in alcoholics.
Excessive alcohol intake frequently results in gastrointestinal discomfort. It is an empirical fact that the severity of gastrointestinal discomfort induced by alcohol abuse is subject to interindividual variation. The aim of this study was to determine whether genetic polymorphism in alcohol dehydrogenase 3 (ADH3) and cytochrome P450 2E1 (CYP2E1), important first-pass enzymes in the metabolism of ethanol, predispose to the development of gastrointestinal symptoms in alcoholics, Blood samples were obtained from 92 adult alcoholics admitted for detoxification. The samples were analyzed for genetic polymorphism in ADH3 and CYP2E1 by polymerase chain reaction followed by restriction fragment length polymorphism analyses. During an interview on the first day of hospital admission, patient characteristics and gastrointestinal symptoms in the week before admission were assessed. A total of 75 of 92 alcoholics (83%) reported symptoms: 66 patients had upper gastrointestinal symptoms (72%), 70 patients had lower gastrointestinal symptoms (76%), and 59 patients reported alarming symptoms (64%). Patients with gastrointestinal symptoms less often abused beer in comparison to those without gastrointestinal symptoms (P = 0.05). The numbers of patients with the homozygous y1y1 genotype, the heterozygous y1y2 genotype, and the homozygous y2y2 genotype in ADH3 who reported gastrointestinal symptoms were 20 (83%), 34 (76%), and 15 (88%), respectively. The number of patients with the heterozygous c1c2 CYP2E1 genotype (5%) and the heterozygous DC CYP2E1 genotype (14%) was low and also unrelated to gastrointestinal symptoms. Our data suggest that the ethanol concentrations of the consumed beverages, and not interindividual variations in the activities of first-pass alcohol-metabolizing enzymes, are associated with gastrointestinal symptoms in alcoholics.
Department of Gastroenterology, University Medical Center St. Radboud, Nijmegen, The Netherlands. R.Laheij@mdl.umcn.nl
R J E
RJ
Laheij
M
M
Verlaan
M G H
MG
Van Oijen
M S
MS
De Doelder
C A J
CA
Dejong
J B M J
JB
Jansen
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000150:complications* / Q000378:metabolism*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D005767:Gastrointestinal Diseases / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
D000431:Ethanol; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1