Gene:
ADH1C
alcohol dehydrogenase 1C (class I), gamma polypeptide

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PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Related Drugs?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs1662060 100259841T>C, 1103+893A>G, 19077A>G, 24807562T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs283411 100265957C>A, 12961G>T, 24813678C>A, 567+62G>T
C > A
Intronic
No VIP available No Clinical Annotations available VA
rs283416 100271356G>A, 19-2353C>T, 24819077G>A, 7562C>T
G > A
Intronic
rs698 100260789T>A, 100260789T>C, 1048A>G, 1048A>T, 18129A>G, 18129A>T, 24808510T>A, 24808510T>C, ADH1C*2, Ile350Phe, Ile350Val
T > C
T > A
Missense
Ile350Val
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  ADH3
Alternate Symbols:  None
PharmGKB Accession Id: PA24572

Details

Cytogenetic Location: chr4 : q23 - q23
GP mRNA Boundary: chr4 : 100257649 - 100273917
GP Gene Boundary: chr4 : 100254649 - 100283917
Strand: minus
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

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. [Article: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 [Articles:16792560, 15099407]. Class I ADHs have high amino acid sequence similarity (~93%) and are clustered on chromosome 4 [Article:11274460]. These enzymes form dimers in vivo and may form heterodimers with other Class I ADHs [Article: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 [Article:15519646].

ADH1C is likely in linkage disequilibrium with ADH1B and therefore does not impact risk of alcoholism independently [Articles:10090900, 14693654]. However, other studies show that ADH1C affects the alcoholism phenotype regardless of ADH1B genotype [Articles:17285601, 17134660].

ADH1C genotypes have been studied in association with laryngeal cancer, but the authors found no conclusive evidence of this association [Article:12668919].

ADH1C*1 is considered to protect against alcoholism because it is a fast acting metabolizer of ethanol, resulting in a build up of acetaldehyde. Compared to the *2 allele, this variant metabolizes ethanol 2.5 times as quickly in vitro [Article:14693654]. The accumulated acetaldehyde results in flushing and other uncomfortable side affects, and typically carriers consume less alcohol accordingly. However, some studies have indicated that this allele has minimal affect on alcohol consumption as compared to ADH1B alleles [Article:16792560]. ADH1C*1 is very common in Asians. In Caucasians, neither the *1 or *2 alleles are the large majority, but heterozygotes are common.

Citation
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
History

Submitted by Michelle Whirl Carrillo

Variant Summaries rs698
Drugs
Drug (1)
Diseases

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Abacavir Pathway, Pharmacokinetics/Pharmacodynamics
    Schematic representation of abacavir metabolism and mechanism of action. The potential mechanism of an abacavir hypersensitivity reaction is also shown.
  1. Cyclophosphamide Pathway, Pharmacodynamics
    Model non-tissue-specific cancer cell displaying genes which may be involved in the cyclophosphamide pathway.
  1. Ifosfamide Pathway, Pharmacodynamics
    Model non-tissue specific cancer cell displaying genes which may be involved in the ifosfamide pathway.

External Pathways

Links to non-PharmGKB pathways.

  1. Ethanol is oxidized by NAD+ to form acetaldehyde, NADH, and H+ - (Reactome via Pathway Interaction Database)
No related genes are available

Curated Information ?

Curated Information ?

Evidence Disease
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Alcoholism
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Ovarian Neoplasms

Publications related to ADH1C: 12

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenomic assessment of cisplatin-based chemotherapy outcomes in ovarian cancer. Pharmacogenomics. 2014. Khrunin Andrey V, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genome-wide significant association between alcohol dependence and a variant in the ADH gene cluster. Addiction biology. 2011. Frank Josef, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Breaking Barriers in the Genomics and Pharmacogenetics of Drug Addiction. Clinical pharmacology and therapeutics. 2010. Ho M K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
ADH single nucleotide polymorphism associations with alcohol metabolism in vivo. Human molecular genetics. 2009. Birley Andrew J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes. The pharmacogenomics journal. 2008. Tolstrup Janne Schurmann, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The ontogeny of drug metabolism enzymes and implications for adverse drug events. Pharmacology & therapeutics. 2008. Hines Ronald N. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Multiple ADH genes modulate risk for drug dependence in both African- and European-Americans. Human molecular genetics. 2007. Luo Xingguang, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Diplotype trend regression analysis of the ADH gene cluster and the ALDH2 gene: multiple significant associations with alcohol dependence. American journal of human genetics. 2006. Luo Xingguang, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. The Proceedings of the Nutrition Society. 2004. Crabb David W, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Pooled analysis of alcohol dehydrogenase genotypes and head and neck cancer: a HuGE review. American journal of epidemiology. 2004. Brennan Paul, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effects of the ADH3, CYP2E1, and GSTP1 genetic polymorphisms on their expressions in Caucasian lung tissue. Lung cancer (Amsterdam, Netherlands). 2002. Yang Mihi, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The RsaI polymorphism of CYP2E1 and susceptibility to alcoholic liver disease in Caucasians: effect on age of presentation and dependence on alcohol dehydrogenase genotype. Pharmacogenetics. 1998. Grove J, et al. PubMed

LinkOuts

Entrez Gene:
126
OMIM:
103730
168600
UCSC Genome Browser:
NM_000669
RefSeq RNA:
NM_000669
RefSeq Protein:
NP_000660
MutDB:
ADH1C
ALFRED:
LO000228M
HuGE:
ADH1C
Comparative Toxicogenomics Database:
126
ModBase:
P00326
HGNC:
251

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