We genotyped the rs1229984 G→A variant of the alcohol dehydrogenase 1B (ADH1B) gene, which is associated with lower prevalence of alcohol abuse and dependence.
Individuals who carry a low-activity ALDH2 (ALDH2*2) display high blood acetaldehyde levels after ethanol consumption, which leads to dysphoric effects, such as facial flushing, nausea, dizziness, and headache ("Asian alcohol phenotype"), which result in an aversion to alcohol and protection against alcohol abuse and alcoholism.
Given the logistic and ethical constraints that would be associated with a trial of alcohol use to prevent depression, we aimed to complete a Mendelian randomization study to determine if a genetic polymorphism associated with alcohol abuse and dependence (ADH1B rs1229984 G-->A) contributed to modulate the risk of depression in a community-derived cohort of older men.
Although the ALDH2*2 allele had a significant inhibitory effect on alcohol consumption, hence on drinking problems, the apparent association was not confirmed between ADH2 genotype and overall drinking patterns for either males or females.
A mutation in the gene encoding for the liver mitochondrial aldehyde dehydrogenase (ALDH2-2), present in some Asian populations, lowers or abolishes the activity of this enzyme and results in elevations in blood acetaldehyde upon ethanol consumption, a phenotype that greatly protects against alcohol abuse and alcoholism.
Among the Atayal, the group with alcohol use disorders (alcohol dependence and alcohol abuse) had a significantly lower frequency of the ADH2*2 allele (0.82) than those without alcohol use disorders (0.91).
As there was a substantial amount of subjects with alcohol abuse between both groups of patients, ADH1B is unlikely to affect the susceptibility to methanol poisoning.
The ALDH2 genotypes consistently and strongly affected the alcohol sensitivity, drinking behavior and problem drinking in both the younger and older group.
The ADH1B genotype was associated with the frequency and volume of drinking but its associations with binge drinking and problem drinking were less consistent.
The ADH1B gene has consistently been implicated in problem drinking, but rarely incorporated into gene by environment investigations of alcohol phenotypes.
The high prevalence of the ALDH2*2 and ADH1B*2 alleles in a large percentage of Asian subgroups has been studied as a potential protective factors against alcohol abuse, yet some individuals who possess these genes still engage in problematic alcohol use (Wall et al.2001).
The ALDH2*2 allele, detected in nearly half of the subjects, showed an overwhelming protective effect against a high level of alcohol consumption and problem drinking behavior, as determined by the Kurihama Alcoholism Screening Test (KAST).
Among conventional markers of alcohol abuse, the mean corpuscular volume (MCV) of erythrocytes is prognostic of alcohol-related cancer and its predictivity increases when combined with functional polymorphisms of alcohol dehydrogenase (ADH1B [rs1229984] and ADH1C [rs698]) and the mitochondrial aldehyde dehydrogenase (ALDH2 [rs671]).
On the other hand, persons with the heterozygous ALDH2*2 genotype (ALDH2*1/2*2) are at higher risk for developing alcohol abuse-related end-organ damage than those with a homozygous ALDH2*1/2*1 genotype.
The primary outcomes were daily alcohol consumption, binge drinking, problem drinking (CAGE score 2+) and smoking status in relation to tagging variants within the FTO and ADH1B genes.