Alcoholism and alcoholic organ damage and genetic polymorphisms of alcohol metabolizing enzymes in Chinese patients.
It is still not clear why some alcoholic patients acquire certain organ-specific complications of alcoholism whereas other alcoholic patients acquire different ones. As we know the liver alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and cytochrome P4502E1 (P4502E1) are polymorphic at the ADH2, ADH3, and ALDH2 loci and the 5'-flanking region of the P4502E1. The aim of this study was to investigate the differences between Chinese alcoholic patients with cirrhosis and acute pancreatitis by studying the genetic polymorphisms of ADH2, ADH3, ALDH2, and P4502E1. Genotyping of ADH2, ADH3, ALDH2, and P4502E1 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods on peripheral white blood cell DNA from 75 alcoholic cirrhotic patients, 48 acute alcoholic pancreatitis patients, 19 heavy drinkers without liver disease or pancreatitis, and 235 controls. The results showed that the frequencies of the alleles ADH2*1 and ALDH2*1 in the alcoholic cirrhotic patients were significantly higher than those in the nonalcoholic controls. In acute alcoholic pancreatitis patients, only the frequency of allele ALDH2*1, not ADH2*1 was significantly higher than in the nonalcoholic controls. The allele frequency of ADH2*1 in acute pancreatitis patients was significantly lower (P < .01) than in alcoholic cirrhotic patients. The daily amount of alcohol consumption was significantly lower in patients with acute pancreatitis than in patients with cirrhosis (P < .0005). The genotype distributions of P4502E1, detected by RsaI and PstI, were not different among alcoholic cirrhotic patients, alcoholic pancreatitis patients, heavy drinker, and nonalcoholic controls. In conclusion, ALDH2*1 is the most important alcohol metabolizing gene affecting predisposition to alcoholism whereas the ADH2*2 gene may influence susceptibility to acute alcoholic pancreatitis. The patients with alcohol-induced cirrhosis and with alcohol-induced acute pancreatitis are of two different subpopulations.
Chao
Y C
YC
Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Young
T H
TH
Tang
H S
HS
Hsu
C T
CT
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000437:Alcoholism / Q000150:complications*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity; D005260:Female; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000209:etiology; D008297:Male; D008875:Middle Aged; D019512:Pancreatitis, Alcoholic / Q000209:etiology; D012150:Polymorphism, Restriction Fragment Length
D000431:Ethanol; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D000444:Aldehyde Dehydrogenase