Annotated PGx Gene Information for ADH1C
Submitted by: Michelle Carrillo (PharmGKB)
Reviewed by: Under Review
Submitted date: March 1, 2008
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| Gene HGNC Name: | ADH1C |
|---|---|
| Gene Common Name: | ADH1C, ADH3, alcohol dehydrogenase gamma subunit |
| Introductory Information: | The ADH1C gene, also commonly referred to in the literature as ADH3, is part of the alcohol dehydrogenase Class I family. Along with ADH1A and ADH1B, ADH1C catalyzes the metabolism of ethanol to acetaldehyde. Aldehyde dehydrogenase (ALDH) converts the resulting acetaldehyde to acetate. Most metabolism of alcohol occurs in the liver, where all Class I ADHs are expressed. [PMID: 14693654] Unlike ADH1A and ADH1B, ADH1C is also expressed in the stomach and intestines, and a limited amount of alcohol metabolism occurs in these organs [PMID: 16792560 15099407]. Class I ADHs have high amino acid sequence similarity (~93%) and are clustered on chromosome 4 [PMID: 11274460]. These enzymes form dimers in vivo and may form heterodimers with other Class I ADHs [PMID: 15099407]. Increased amounts of acetaldehyde are associated with adverse reactions to alcohol such as flushing, nausea and headaches. The slowed conversion of acetaldehyde to acetate due to reduced function ALDH enzymes and the rapid metabolism of alcohol to acetaldehyde both can lead to acetaldehyde build up. The *1 allele of ADH1C displays more rapid metabolism of ethanol to acetaldehyde than the *2 allele and is therefore associated with these symptoms. It is generally accepted that these adverse reactions to alcohol lead to limited alcohol consumption and subsequently protection against alcoholism. However, at least one study (in a Spanish population) found no protection from alcoholism or liver disease based on ADH1C genotype [PMID: 15519646]. ADH1C is likely in linkage disequilibrium with ADH1B and therefore does not impact risk of alcoholism independently [PMID: 10090900 14693654]. However, other studies show that ADH1C affects the alcoholism phenotype regardless of ADH1B genotype [PMID: 17285601 17134660]. ADH1C genotypes have been studied in association with laryngeal cancer, but the authors found no conclusive evidence of this association [PMID: 12668919]. |
| Key PubMed IDs: | 1509940714693654 |
| Key Pathways: | NA |
| Drugs/Substrates: | alcohol |
| Phenotypes/Diseases: | Alcoholism |
| Important Variants: | ADH1C*1 ADH1C*2 |