Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism

Area of Science:

• Biochemistry
• Genetics
• Pharmacology

Background:

• The alcohol-flush reaction, common in East Asians, is associated with the ALDH2*2 allele, leading to inactive aldehyde dehydrogenase.
• High blood acetaldehyde levels from impaired metabolism are considered the cause of flushing and discomfort after alcohol consumption.

Purpose of the Study:

• To investigate the relationship between alcohol dehydrogenase (ADH2, ADH3) and aldehyde dehydrogenase (ALDH2) genotypes and alcohol metabolism.
• To correlate these genotypes with the intensity of alcohol-flush reaction and drinking behavior in Chinese subjects.

Main Methods:

• Genotyping for ADH2, ADH3, and ALDH2 alleles in 100 Chinese men.
• Measurement of alcohol elimination rates and assessment of flushing intensity.
• Correlation analysis between genotypes and drinking behavior.

Main Results:

• Alleles ADH2*2, ADH3*1 (high ADH activity), and ALDH2*2 (inactive ALDH) were less frequent in alcoholics compared to controls.
• The ALDH2*2 allele was associated with slower alcohol metabolism and more intense flushing.
• In ALDH2*1 homozygous individuals, the presence of two ADH2*2 alleles correlated with slightly faster alcohol metabolism and increased flushing intensity, though with significant variability.

Conclusions:

• Alcohol metabolism and flush reaction intensity are significantly influenced by ADH and ALDH2 genotypes.
• The ALDH2*2 allele plays a crucial role in alcohol metabolism and the severity of the alcohol-flush reaction.
• Genetic variations in alcohol-metabolizing enzymes impact drinking behavior and susceptibility to alcohol-related flushing.