Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism.
Level 4 - case-series / case-control
Case-control genetic association study
PubMed 10441588 · doi:10.1086/302540
What was done
A case-control genetic association study genotyped 340 alcoholic and 545 control Han Chinese individuals living in Taiwan at three functional polymorphic loci: ADH2, ADH3, and ALDH2. Multiple logistic regression analysis was performed to test for independent effects and interactions among combinatorial genotypes on the risk of alcoholism.
What was found
ALDH2*2 homozygosity was entirely protective against alcoholism regardless of ADH2 genotype (0 individuals found among the 340 alcoholic cases). When controlling for ALDH2*2, ADH3 variation showed no significant effect due to linkage disequilibrium with ADH2*2. Compared to the reference ADH2*1/*1 and ALDH2*1/*1 genotype, individuals with one or two copies of ADH2*2 plus a single ALDH2*2 copy had the lowest risk of alcoholism (ORs 0.04-0.05). Risk for the ADH2*2/*2-ALDH2*1/*1 genotype was approximately half that of ADH2*1/*2-ALDH2*1/*1.
Why it matters
The findings demonstrate that ADH2*2 and ALDH2*2 provide independent protective effects against alcoholism, while clarifying that ADH3 does not independently contribute.
Limits
The study is restricted to a single ethnic group (Han Chinese in Taiwan). As a case-control design, it is susceptible to selection bias, and the abstract does not report confidence intervals, exact p-values, or clinical diagnostic criteria for alcoholism.
Cited by
- supports Many Han Chinese individuals lack or have low levels of the enzyme that breaks down acetaldehyde into acetic acid during alcohol metabolism, making alcohol consumption less pleasant and specifically lowering their risk for alcoholism.