Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes

Abstract

Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1-11) among men with the ADH1B Á 1/1 genotype compared to 7.5 drinks (95% CI: 6.4-8.7) among men with the ADH1B Á 1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7-5.7) among men with the ADH1B Á 1/1 genotype compared to men with the ADH1B Á 1/2 genotype. Furthermore, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1-1.8) among men with the ADH1C Á 1/2 genotype and 1.4 (95% CI: 1.0-1.9) among men with the ADH1B Á 2/2 genotype, compared with men with the ADH1C Á 1/1 genotype. Results for ADH1B and ADH1C genotypes among men and women were similar. Finally, because slow ADH1B alcohol degradation is found in more than 90% of the white population compared to less than 10% of East Asians, the population attributable risk of heavy drinking and alcoholism by ADH1B Á 1/1 genotype was 67 and 62% among the white population compared with 9 and 24% among the East Asian population.

Immunoglobulin E Sensitization to Cross-Reactive Carbohydrate Determinants: Epidemiological Study of Clinical Relevance and Role of Alcohol Consumption

“…Interestingly, acetaldehyde is responsible for the abnormal protein glycosylation that is commonly observed in alcohol abusers [31,32]. The ADH1b polymorphism has a much stronger effect on the rate of conversion of alcohol to acetaldehyde than the ADH1c polymorphism [29,30], which may explain why we only found an association between CCD sensitization and the ADH1b, and not the ADH1c, polymorphism. Furthermore, the low frequency of the A allele of the ADH1b polymorphism and the fact that none of the participants was found to be homozygote for this allele made it impossible to investigate a potential dose-response effect.…”

“…The biological mechanisms underlying alcohol-induced CCD sensitization are not clear. Individuals carrying the A-allele of the ADH1b polymorphism are faster metabolizers of ethanol compared to those who are homozygotous for the wild-type allele (the G-allele) [29,30]. Fast metabolizers experience higher peak levels of acetetaldehyde following alcohol drinking.…”

Genetic Variants Associated With Myocardial Infarction Risk Factors in Over 8000 Individuals From Five Ethnic Groups

“…For rs1433099 after adjusting for Apo B/A1, the P value becomes P ϭ 0.0065; OR ϭ 0.91, 95% CI: 0.85 to 0.97, and after adjusting for all 9 risk factors the P value becomes 0.0039, OR ϭ 0.89, 95% CI: 0.83 to 0.96. previously reported. 25 In addition, variants in this gene have also been associated with alcohol dependence 26 and alcoholism, 25 and they are known to display large differences in allele frequency among populations. 27 Genetic variants at this locus have also been identified that interact with alcohol consumption to increase heart disease.…”

Role of UGT1A1 and ADH gene polymorphisms in pegvisomant-induced liver toxicity in acromegalic patients

“…The biliary and liver metabolism of biological molecules associated with polyethylene glycol suggests a possible involvement of ADH enzymes in PEG-V metabolism. Interestingly, some ADH1B and 1C polymorphisms have been associated with alcohol pharmacokinetics, alcoholism, and alcoholic hepatopathy (12,13,14,15,16). On this basis, this study was carried out to evaluate whether polymorphic variants of UGT1A1 and ADH genes may be associated with mild or severe liver disease in acromegalic patients during PEG-V treatment.…”

“…In addition, biliary excretion and polyethylene glycol metabolism by alcohol dehydrogenase (ADH) have been described in humans (11). As pharmacogenetics studies on normal subjects and on patients with alcohol abuse showed a role of some ADH1B and 1C gene polymorphisms in ethanol pharmacokinetics and hepatopathy (12,13,14,15,16), the aim of this study was to evaluate possible associations between PEG-V-induced liver injury and the previously reported UGT1A1*28 variant and additionally with some ADH polymorphisms involved in liver disorders or alcohol metabolism.…”