Polymorphism of alcohol and aldehyde dehydrogenase genes and alcoholic cirrhosis in chinese patients

Abstract

Liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the principal enzymes responsible for the oxidation of ethanol, are polymorphic at the ADH2, ADH3 and ALDH2 loci in human beings. Our previous studies have shown that, compared with nonalcoholic individuals, Chinese alcoholic patients without liver disease had significantly lower frequencies of the ADH2*2 and ADH3*1 alleles, which encode high maximum velocity beta 2- and gamma 1-ADH subunits, respectively, as well as a lower frequency of the ALDH2*2 allele, which encodes an enzymatically inactive subunit. The data strongly suggest that genetic variation in both ADH and ALDH may influence drinking behavior and the risk of alcoholism developing through acetaldehyde formation. To further investigate the possible role of acetaldehyde in the pathogenesis of alcoholic liver disease, we determined the ADH and ALDH genotype frequencies in patients with alcohol-related cirrhosis (n = 27), viral hepatitis-related cirrhosis (n = 29) and gastric and duodenal ulcer without relevance to alcohol (n = 30). We developed a new restriction fragment length polymorphism method to genotype the mutant and normal ALDH2 alleles by using polymerase chain reaction-directed mutagenesis, which proved to be simpler and faster than the conventional detection methods that use hybridization with allele-specific oligonucleotide probes. We found that the frequencies of the alleles ADH2*2 (57%), ADH3*1 (78%) and ALDH2*2 (9%) in the alcoholic cirrhotic patients were significantly lower than those in the healthy controls and in the patients with cirrhosis from viral hepatitis and with gastric and duodenal ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)

RETRACTED: Aldehyde dedydrogenase-2 plays a beneficial role in ameliorating chronic alcohol-induced hepatic steatosis and inflammation through regulation of autophagy

“…However, the precise mechanism(s) of action behind this mitochondrial enzyme-induced reversal against alcohol-induced hepatic injury remains elusive. Epidemiological evidence has suggested a tie between polymorphisms of genes involved in the metabolism of alcohol including ALDH2 and alcoholic liver diseases [32-35]. Liver injury may be caused by direct toxicity of alcohol or its metabolic byproducts, as well as by inflammation induced by these byproducts[27].…”

Association of ADHIB and ALDH2gene polymorphisms with alcohol dependence: A pilot study from India

“…[29] reported that the homozygous ALDH2*2/*2 genotype is present at a very low frequency (0-0.3 per cent) in alcoholic patients, compared with 3-12 per cent among non-alcoholic subjects. The heterozygous ALDH2*1/*2 genotype has been found to be present in 6-17 per cent of alcohol-dependent subjects, compared with 30-45 per cent of non-alcoholic subjects [5,33,34]. This difference in ALDH2*2 allele frequency between alcoholic and non-alcoholic subjects has been postulated to be responsible for the phenomenon of adverse responses to alcohol consumption, such as facial flushing, nausea and tachycardia in individuals with the inactive form of the enzyme [29].…”

Addiction, Chronic Illness, and Responsibility

“…Tolerance (or intolerance) for alcohol, for example, appears heritable (cf. Chao et al 1994;Newmark et al 1998;Schuckit 1994;Schuckit and Smith 1996). However, the risk factors for diabetes and hypertension (e.g., obesity, stress, and inactivity) are also all strongly linked to family traditions, culture, and personal preferences (cf.…”