Annotated PGx Gene Information for ADH1B
Submitted by: Michelle Carrillo (PharmGKB)
Reviewed by: Under Review
Submitted date: March 1, 2008
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| Gene HGNC Name: | ADH1B |
|---|---|
| Gene Common Name: | ADH1B, ADH2, alcohol dehydrogenase beta subunit |
| Introductory Information: | ADH1B, also commonly known as ADH2 or ADH beta, is a Class I alcohol dehydrogenase gene. Alcohol dehydrogenases metabolize ethanol to acetaldehyde, which is subsequently metabolized by aldehyde dehydrogenases (ALDH1A, ALDH2 genes) to acetate. This metabolism occurs primarily in the liver [PMID: 14693654]. The Class I alcohol dehydrogenase family is comprised of ADH1A, ADH1B and ADH1C. Collectively, the Class I ADHs are responsible for the metabolism of about 70% of ethanol in the liver at a concentration of approximately 22mM [PMID: 16571603]. The Class I ADHs are very similar genes; each is approximately 15 kb in size, and the resulting proteins share a 93% amino acid sequence identity [PMID: 11274460]. All three Class I genes are clustered on chromosome 4, specifically in the region 4q22 [PMID: 15099407 16571603]. This class of ADHs is inhibited by pyrazole and its derivatives [PMID: 15099407]. ADH1B is expressed predominantly in the liver [PMID: 16792560]. The Km and Vmax values for ethanol as a substrate for ADH1B vary widely depending on the allele of ADH1B, with the *1 allele displaying the lowest Km and Vmax [PMID: 15099407]. The ADH1B*1 protein structure has been elucidated by x-ray crystallography, and a binding site has been localized near the zinc atom. The ADH1B*1 binding site is predicted to be more restrictive than either ADH1A or ADH1C*2 [PMID: 11274460]. In vivo, ADH1B exists as a dimer [PMID: 10441588]. It can either form homodimers or heterodimers with other class 1 ADHs [PMID: 15099407]. ADH1B*2 and ADH1C*1 are responsible for a more rapid metabolism of alcohol than the other ADH1B and ADH1C alleles. There are conflicting studies as to whether these alleles are in linkage disequilibrium [PMID: 10441588]. A study of three different Taiwanese populations found the genes to be in linkage disequilibrium [PMID: 10090900], and LD has also been found in several Caucasian populations [PMID: 14693654]. However, in other studies, the effect of ADH1C*1 is independent of the ADH1B*2 allele. One study analyzing the drinking habits of Japanese men found this to be the case [PMID: 17285601]. Another study focusing on a population from Trinidad and Tobago also found independence between ADH1B and ADH1C [PMID: 17134660]. ADH1B has been studied with conflicting results in association with Fetal Alcohol Syndrome, oral cancer, esophageal cancer, colorectal cancer, testicular atrophy and breast cancer [PMID: 15099407]. ADH1B genotype has been linked to esophageal cancer along with ALDH2 [PMID: 17036331]. In another study, ADH1B genotype did not correlate with the risk of laryngeal cancer in a population of Caucasian Germans [PMID: 12668919]. In yet another study, no correlation was found between ADH1B or ADH1C genotype and alcoholism or liver disease in a Spanish male population [PMID: 15519646]. ADH1B has been thought to be secondary in importance to ALDH2 in the metabolic conversion of ethanol to acetate. However, at least two studies suggest that protection from alcoholism may affected by ADH1B independently of ALDH2 [PMID: 10441588 16086315]. |
| Key PubMed IDs: | 16571603 14693654 15099407 |
| Key Pathways: | NA |
| Drugs/Substrates: | alcohol |
| Phenotypes/Diseases: | Alcoholism |
| Important Variants: | ADH1B*1 ADH1B*2 ADH1B*3 |