Molecular genetics of human aldehyde dehydrogenase
1Department of Biochemical Genetics, Beckman Research Institute of the City of Hope, Duarte, CA 91010.
Pharmacogenetics
|August 1, 1992
Summary
Genetic variations in aldehyde dehydrogenase (ALDH) genes influence alcohol metabolism and disease risk. ALDH2 variations, common in Orientals, confer alcohol sensitivity and reduce alcoholism risk.
Area of Science:
- Biochemistry
- Genetics
- Pharmacology
Background:
- Four non-allelic genes encode distinct aldehyde dehydrogenase (ALDH) isozymes.
- These genes (ALDH1, ALDH2, ALDH3, ALDH5) have been cloned and characterized, with their nucleotide sequences and gene organization elucidated.
Purpose of the Study:
- To characterize four ALDH isozymes and their corresponding genes.
- To investigate the genetic variations and frequencies of ALDH genes in different populations.
- To explore the relationship between ALDH gene variations and alcohol-related traits.
Main Methods:
- Gene cloning and characterization.
- Nucleotide sequencing and analysis of intron-exon organization.
- Population genetic studies to determine allele frequencies.
Main Results:
- ALDH1 deficiency is rare (<10%) in Caucasians and Orientals, with deficiency linked to alcohol sensitivity in one family.
- A common ALDH2(2) allele (~30%) in Orientals results in absent ALDH activity, conferring alcohol sensitivity and reduced risk of alcoholism and liver disease.
- ALDH3 is found in stomach/liver carcinoma but not normal liver and is polymorphic.
- ALDH5 is polymorphic in both Caucasians and Orientals and expressed in testes and liver.
Conclusions:
- ALDH gene variations, particularly in ALDH2, significantly impact alcohol metabolism and susceptibility to alcohol-related disorders.
- ALDH2 deficiency is a protective factor against alcoholism and alcoholic liver disease in Oriental populations.
- Polymorphisms in ALDH3 and ALDH5 may also influence alcohol-related problem development.
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