Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant ALDH2*2 Gene Allele.

Yi-Chyan Chen,Shih-Jiun Yin,Li-Fang Yang,Ching-Long Lai

doi:10.3390/biom11081183

Abstract

Alcoholism is a complex behavior trait influenced by multiple genes as well as by sociocultural factors. Alcohol metabolism is one of the biological determinants that can significantly influence drinking behaviors. Alcohol sensitivity is thought to be a behavioral trait marker for susceptibility to develop alcoholism. The subjective perceptions would be an indicator for the alcohol preference. To investigate alcohol sensitivity for the variants ADH1B*2 and ALDH2*2, sixty healthy young males with different combinatory ADH1B and ALDH2 genotypes, ADH1B*2/*2–ALDH2*1/*1 (n = 23), ADH1B*2/*2–ALDH2*1/*2 (n = 27), and ADH1B*1/*1–ALDH2*1/*1 (n = 10), participated in the study. The subjective perceptions were assessed by a structured scale, and blood ethanol and acetaldehyde were determined by GC and HPLC after an alcohol challenge in two dose sessions (0.3 g/kg or 0.5 g/kg ethanol). The principal findings are (1) dose-dependent increase of blood ethanol concentration, unaffected by ADH1B or ALDH2; (2) significant build-up of blood acetaldehyde, strikingly influenced by the ALDH2*2 gene allele and correlated with the dose of ingested alcohol; (3) the increased heart rate and subjective sensations caused by acetaldehyde accumulation in the ALDH2*2 heterozygotes; (4) no significant effect of ADH1B polymorphism in alcohol metabolism or producing the psychological responses. The study findings provide the evidence of acetaldehyde potentiating the alcohol sensitivity and feedback to self-control the drinking amount. The results indicate that ALDH2*2 plays a major role for acetaldehyde-related physiological negative responses and prove the genetic protection against development of alcoholism in East Asians.

Highlights

Alcoholism is one of most common mental disorders and cause devastating medical complications and social negative impacts
The principal findings have shown the following: (1) dose-dependent increase of blood ethanol concentration, unaffected by ADH1B or ALDH2; (2) significant build-up of blood acetaldehyde, strikingly influenced by the ALDH2*2 gene allele and correlated with the dose of ingested alcohol; (3) the increased heart rate and subjective sensations caused by acetaldehyde accumulation in the ALDH2*1/*2 heterozygotes; (4) no significant effect of ADH1B polymorphism in alcohol metabolism or producing the psychological responses
The alterations of subjective perceptions in ALDH2*1/*2 healthy participants after challenge with different ethanol doses have shown to be primarily caused by the accumulation of acetaldehyde, rather than ethanol

Summary

Introduction

Alcoholism is one of most common mental disorders and cause devastating medical complications and social negative impacts. Alcohol-related disease morbidity and mortality markedly increased in the youngest age group and adulthood [1]. Problematic drinking is a major public health issue, directly leading to physical dysfunction and shortening life expectancy [2]. Animal, and clinical studies demonstrated that alcoholism is believed to be a multifactorial, polygenic disorder involving complex gene-to-gene and gene-toenvironment interactions. Alcohol metabolism is one of the biological determinants that can significantly influence the drinking behavior and the development of alcoholism [3,4,5,6]. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the key enzymes responsible for ethanol metabolism through first-pass metabolism in the liver [3,7,8,9,10]

Methods

Results

Discussion

Conclusion