ALDH2 Lys alleles had a higher risk with increased alcohol consumption compared with ALDH2 Glu/Glu (OR for heavy drinking, 3.57; 95% CI 2.04-6.27; P for trend = 0.007), indicating a significant ALDH2-alcohol drinking interaction (P<sub>interaction</sub> = 0.024).
Our findings suggest that the interplay between ALDH2∗2 and drinking-related problems is complex, involving both mediation and moderation processes that reduce the likelihood of developing problems via reduction of heavy drinking as well as by altering the relationship between alcohol consumption and problems.
Multiple logistic regression analyses revealed that the ALDH2*2 variant allele was an independent variable exhibiting strong protection (odds ratio 0.072; 95 per cent confidence interval 0.02-0.26) against HDS after adjustment for hypertension, diabetes mellitus, smoking status and liver dysfunction.
These results suggest that both inactive and active forms of ALDH2 are induced in the esophagus by heavy drinking and also support a hypothesis that ALDH2 deficiency might be a high-risk factor of esophageal cancer for the individuals having a heavy-drinking habit.
ALDH inactive form resulting from ALDH2*2, which slows the elimination of acetaldehyde and the more active isozymes produced by ADH1B*2, could generate higher acetaldehyde levels and thus deter heavy drinking ().
This low-dose alcohol hypersensitivity, accompanied by a prolonged and large accumulation of acetaldehyde in blood, provides an explanation for the strong protection against heavy drinking and alcoholism in individuals homozygous for the ALDH2*2 gene allele.
Approximately 10% of Japanese alcoholics develop their disease despite having an inactive form of aldehyde dehydrogenase-2 (ALDH2), known as a genetic deterrent of heavy drinking due to adverse reactions after drinking.
Inactive aldehyde dehydrogenase-2 (ALDH2) is a well-known biological deterrent of heavy drinking among Asians, although some individuals who have inactive ALDH2 do become alcoholics.