ALDH2*2 but not ADH1B*2 is a causative variant gene allele for Asian alcohol flushing after a low-dose challenge: correlation of the pharmacokinetic and pharmacodynamic findings.
Level 3 - non-randomized controlled study
Controlled non-randomized pharmacogenetic challenge study comparing defined genotypic groups
PubMed 25365528 · doi:10.1097/FPC.0000000000000096
What was done
Sixty-one adult Han Chinese men were classified into six combinatorial genotype groups based on ALDH2 (*1/*1 or *1/*2) and ADH1B (*1/*1, *1/*2, or *2/*2) alleles (subgroup sizes ranged from 9 to 12). Participants consumed a low dose of alcohol (0.3 g/kg). Blood concentrations of ethanol, acetaldehyde, and acetate, along with facial skin blood flow (FSBF) and pulse rate, were monitored over a 130-minute period.
What was found
The abstract does not report raw numerical values. ALDH2*1/*2 heterozygotes demonstrated significantly higher peak levels and area under the concentration curve (AUC) for blood acetaldehyde, as well as significantly greater peak increases in pulse rate and FSBF compared with ALDH2*1/*1 homozygotes across all ADH1B backgrounds. In contrast, no significant differences in ethanol, acetaldehyde, or acetate levels, or cardiovascular responses, were found among different ADH1B allelotypes within either ALDH2 group. Partial correlation analysis showed that peak blood acetaldehyde, rather than ethanol or acetate, correlated significantly with peak FSBF and pulse rate changes.
Why it matters
This study clarifies the genetic mechanism of Asian alcohol flushing, demonstrating that impaired acetaldehyde clearance from ALDH2*2, rather than altered ethanol oxidation from ADH1B*2, is responsible for systemic acetaldehyde accumulation and acute cardiovascular responses at low alcohol doses.
Limits
The sample size is modest with only 9 to 12 participants per genotype subgroup. The study included exclusively adult Han Chinese men, limiting generalizability to females and other ethnic groups. Only a single low dose of alcohol (0.3 g/kg) was evaluated, and ALDH2*2/*2 homozygotes were not included.
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.