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

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...

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Main Authors: Yi-Chyan Chen, Li-Fang Yang, Ching-Long Lai, Shih-Jiun Yin
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/11/8/1183
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author Yi-Chyan Chen
Li-Fang Yang
Ching-Long Lai
Shih-Jiun Yin
author_facet Yi-Chyan Chen
Li-Fang Yang
Ching-Long Lai
Shih-Jiun Yin
author_sort Yi-Chyan Chen
collection DOAJ
description 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 <i>ADH1B*2</i> and <i>ALDH2*2</i>, sixty healthy young males with different combinatory <i>ADH1B</i> and <i>ALDH2</i> genotypes, <i>ADH1B*2/*2–ALDH2*1/*1</i> (<i>n</i> = 23), <i>ADH1B*2/*2–ALDH2*1/*2</i> (<i>n</i> = 27), and <i>ADH1B*1/*1–ALDH2*1/*1</i> (<i>n</i> = 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 <i>ADH1B</i> or <i>ALDH2</i>; (2) significant build-up of blood acetaldehyde, strikingly influenced by the <i>ALDH2*2</i> gene allele and correlated with the dose of ingested alcohol; (3) the increased heart rate and subjective sensations caused by acetaldehyde accumulation in the <i>ALDH2*2</i> heterozygotes; (4) no significant effect of <i>ADH1B</i> 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 <i>ALDH2*2</i> plays a major role for acetaldehyde-related physiological negative responses and prove the genetic protection against development of alcoholism in East Asians.
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spelling doaj.art-8c0c06d075b340698e8e151a115541d22023-11-22T06:56:00ZengMDPI AGBiomolecules2218-273X2021-08-01118118310.3390/biom11081183Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant <i>ALDH2*2</i> Gene AlleleYi-Chyan Chen0Li-Fang Yang1Ching-Long Lai2Shih-Jiun Yin3Department of Psychiatry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, TaiwanDepartment of Psychiatry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, TaiwanDepartment of Nursing and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan 333, TaiwanDepartment of Biochemistry, National Defense Medical Center, Taipei 114, TaiwanAlcoholism 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 <i>ADH1B*2</i> and <i>ALDH2*2</i>, sixty healthy young males with different combinatory <i>ADH1B</i> and <i>ALDH2</i> genotypes, <i>ADH1B*2/*2–ALDH2*1/*1</i> (<i>n</i> = 23), <i>ADH1B*2/*2–ALDH2*1/*2</i> (<i>n</i> = 27), and <i>ADH1B*1/*1–ALDH2*1/*1</i> (<i>n</i> = 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 <i>ADH1B</i> or <i>ALDH2</i>; (2) significant build-up of blood acetaldehyde, strikingly influenced by the <i>ALDH2*2</i> gene allele and correlated with the dose of ingested alcohol; (3) the increased heart rate and subjective sensations caused by acetaldehyde accumulation in the <i>ALDH2*2</i> heterozygotes; (4) no significant effect of <i>ADH1B</i> 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 <i>ALDH2*2</i> plays a major role for acetaldehyde-related physiological negative responses and prove the genetic protection against development of alcoholism in East Asians.https://www.mdpi.com/2218-273X/11/8/1183alcohol metabolismgenetic variation<i>ALDH2*2</i>ethanolacetaldehydealcohol sensitivity
spellingShingle Yi-Chyan Chen
Li-Fang Yang
Ching-Long Lai
Shih-Jiun Yin
Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant <i>ALDH2*2</i> Gene Allele
Biomolecules
alcohol metabolism
genetic variation
<i>ALDH2*2</i>
ethanol
acetaldehyde
alcohol sensitivity
title Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant <i>ALDH2*2</i> Gene Allele
title_full Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant <i>ALDH2*2</i> Gene Allele
title_fullStr Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant <i>ALDH2*2</i> Gene Allele
title_full_unstemmed Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant <i>ALDH2*2</i> Gene Allele
title_short Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with Variant <i>ALDH2*2</i> Gene Allele
title_sort acetaldehyde enhances alcohol sensitivity and protects against alcoholism evidence from alcohol metabolism in subjects with variant i aldh2 2 i gene allele
topic alcohol metabolism
genetic variation
<i>ALDH2*2</i>
ethanol
acetaldehyde
alcohol sensitivity
url https://www.mdpi.com/2218-273X/11/8/1183
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