Genotypes of alcohol-metabolizing enzymes and the risk for alcoholic chronic pancreatitis in Japanese alcoholics.
Genetic predisposition to alcoholism and alcoholic liver disease has been reported. However, genetic susceptibility to alcoholic pancreatitis is still a matter of debate. To determine it, we examined genotype patterns of aldehyde dehydrogenase (ALDH2), alcohol dehydrogenase (ADH2 and ADH3), and cytochrome P-4502E1 (CYP2E1) in alcoholic pancreatitis patients. In 296 alcoholic patients, 52 cases showed findings of chronic pancreatitis by ultrasonography and x-ray computed tomography and/or had a history of pancreatitis (P+). The remaining 244 patients had neither abnormal findings of the image examinations nor a history of pancreatitis (P-). As for the ADH2 genotype, distribution of 2(1)/2(1), 2(1)/2(2), and 2(2)/2(2) was 22, 37, and 42% in P+ patients, whereas 34, 35, and 30% in P- patients, respectively. The frequency of ADH2(2)/2(2) genotype was significantly higher in P+ patients, compared with that in P- patients. There were no significant differences in the distribution of ADH3, ALDH2, and CYP2E1 genotypes between P+ and P- patients. In 14 alcoholic patients who showed low contents of fecal chymotrypsin, which suggests dysfunction of pancreatic exocrine, the rate of ADH2(2)/2(2) genotype also tended to be higher (50%) than in 74 controls who showed normal contents of the fecal chymotrypsin (28%). No differences were observed in genotypes of ADH3, ALDH2, and CYP2E1. Moreover, the frequency of ADH2(2)/2(2) genotype was significantly higher in autopsy cases with interlobular fibrosis in the pancreas, which suggests alcoholic pancreatic damage, than in cases with only intralobular pancreatic fibrosis. These data suggest that the risk of alcoholic pancreatitis seems to be associated with the presence of ADH2(2)/2(2) genotype.
Matsumoto
M
M
Department of Internal Medicine, Kurihama National Hospital, National Institute on Alcoholism, Yokosuka, Japan.
Takahashi
H
H
Maruyama
K
K
Higuchi
S
S
Matsushita
S
S
Muramatsu
T
T
Okuyama
K
K
Yokoyama
A
A
Nakano
M
M
Ishii
H
H
D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000502:physiology; D000437:Alcoholism / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000502:physiology; D002908:Chronic Disease; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics* / Q000502:physiology; D000431:Ethanol / Q000493:pharmacokinetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000502:physiology; D007564:Japan; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000201:enzymology / Q000473:pathology; D019512:Pancreatitis, Alcoholic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
D007527:Isoenzymes; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D000444:Aldehyde Dehydrogenase