Long-term consumption of large amounts of alcohol is the main cause of
chronic pancreatitis. All heavy drinkers, however, do not contract
chronic pancreatitis. Although
genetic predisposition to
alcoholism and
alcoholic liver disease has been reported,
genetic susceptibility to
alcoholic pancreatitis is still a matter of debate. To determine the relation between genotypes of alcohol-metabolizing
enzymes and chronic
alcoholic pancreatitis, we examined genotype patterns of
aldehyde dehydrogenase 2 (ALDH 2),
alcohol dehydrogenase 2 (ADH 2) and
cytochrome P-4502E1 (
CYP2E1) in 54 patients with chronic
alcoholic pancreatitis who were diagnosed in general hospitals in all over Japan and compared with those in 30 patients with chronic nonalcoholic
pancreatitis or in 46 alcoholics with normal pancreatic function. There were no significant differences in the distribution of genotypes of ALDH 2 and
CYP2E1 among those three groups. As for the ADH 2 genotype, distribution of 2(1)/2(1), 2(1)/2(2), and 2(2)/2(2) was 35%, 30%, and 35% in alcoholics with normal pancreatic function; 4%, 39%, and 57% in the chronic
alcoholic pancreatitis group; and 0%, 50%, and 50% in the chronic nonalcoholic
pancreatitis group, respectively. The frequency of ADH 2(2) allele was significantly higher in the chronic
alcoholic pancreatitis group, compared with alcoholics with normal pancreatic function; but, it was not significantly different from that in the chronic nonalcoholic
pancreatitis group. We also examined the relation between pancreatic
fibrosis or
pancreatitis histologically diagnosed and genotypes of alcohol-metabolizing
enzymes in alcoholic autopsy cases. Twenty of 31 cases showed moderate or severe pancreatic
fibrosis and showed intralobular + interlobular
fibrosis, which is characteristic in
alcoholic pancreatitis or intralobular
fibrosis. ADH 2(2) allele tended to show a high frequency in the intralobular + interlobular
fibrosis group, compared with that in the intralobular
fibrosis group (75.0% vs. 41.7%, p < 0.1). The
chronic pancreatitis group had a significantly higher frequency of the ADH 2(2) allele than that in cases without such findings (87.5% vs. 58.7%, p < 0.05). However, the ALDH 2 and
CYP2E1 genotypes showed no significant relation to the findings of pancreatic
fibrosis or histological
pancreatitis. These data suggest that the risk of chronic
alcoholic pancreatitis diagnosed clinically and pathologically seems to be associated with the ADH 2(2) allele in the genotypes of alcohol-metabolizing
enzymes.