Gene:
BCHE
butyrylcholinesterase

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.


FDA Label for succinylcholine and BCHE, CACNA1S, RYR1

Summary

Succinylcholine is rapid acting, depolarizing skeletal muscle relaxant indicated as an adjunct to general anesthesia, to facilitate tracheal intubation and mechanical ventilation. The FDA label warns that individuals who are carriers of the atypical variant of the plasma cholinesterase gene (BCHE) are at risk of prolonged apnea if administered succinylcholine, contraindicates succinylcholine in individuals diagnosed with Duchene's or Becker's muscular dystrophy because of risk of rhabdomyolysis, hyperkalemia and cardiac arrest and contraindicates succinylcholine in individuals with a family history of malignant hyperthermia, a potentially fatal hypermetabolic state in skeletal muscle.

Annotation

Annotation

Although the succinylcholine chloride (Anectine) drug label does not specifically mention genetic testing, the FDA highlights that precaution should be taken prior to administering succinylcholine for individuals carrying one of many genetic variants known to increase the risk of:

  • Prolonged apnea
  • Malignant hyperthermia
  • Hyperkalemia

Specific variants in the RYR1 and CACNA1S genes are associated with risk of malignant hyperthermia in individuals administered succinylcholine. The currently accepted standard for testing for susceptibility to malignant hyperthermia is the in vitro contracture test (also known as the caffeine halothane contracture test).

Excerpts from the succinylcholine chloride (Anectine) drug label:


RISK OF CARDIAC ARREST FROM HYPERKALEMIC RHABDOMYOLYSIS
There have been rare reports of acute rhabdomyolysis with hyperkalemia followed by ventricular dysrhythmias, cardiac arrest, and death after the administration of succinylcholine to apparently healthy children who were subsequently found to have undiagnosed skeletal muscle myopathy, most frequently Duchenne's muscular dystrophy.

Succinylcholine is contraindicated in persons with personal or familial history of malignant hyperthermia, skeletal muscle myopathies, and known hypersensitivity to the drug.

WARNINGS
SUCCINYLCHOLINE IS METABOLIZED BY PLASMA CHOLINESTERASE AND SHOULD BE USED WITH CAUTION, IF AT ALL, IN PATIENTS KNOWN TO BE OR SUSPECTED OF BEING HOMOZYGOUS FOR THE ATYPICAL PLASMA CHOLINESTERASE GENE.

Patients homozygous for atypical plasma cholinesterase gene (1 in 2500 patients) are extremely sensitive to the neuromuscular blocking effect of succinylcholine. In these patients, a 5- to 10-mg test dose of succinylcholine may be administered to evaluate sensitivity to succinylcholine, or neuromuscular blockade may be produced by the cautious administration of a 1-mg/mL solution of succinylcholine by slow IV infusion. Apnea or prolonged muscle paralysis should be treated with controlled respiration.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the succinylcholine chloride drug label.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Apnea
    • Warnings section, Pediatric use section, Adverse reactions section, Precautions section, other
    • source: FDA Label
  • Hyperkalemia
    • Boxed warning section, Contraindications section, Pediatric use section, Adverse reactions section, Warnings and precautions section, other
    • source: FDA Label
  • Malignant Hyperthermia
    • Boxed warning section, Contraindications section, Warnings section, Pediatric use section, Adverse reactions section, other
    • source: FDA Label
  • BCHE
    • Adverse reactions section, Warnings and precautions section, other
    • source: FDA Label

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.

? = Mouse-over for quick help

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 CA VA
rs1799807 11725A>G, 165548529T>C, 293A>G, 72043675T>C, Asp98Gly, BCHE: dibucaine-resistant variant, BCHE:209A>G, BCHE:Asp70Gly, BCHE:atypical variant
T > C
Missense
Asp98Gly
No VIP available CA VA
rs1803274 165491280C>T, 1699G>A, 68974G>A, 71986426C>T, Ala567Thr
C > T
Missense
Ala567Thr
No VIP available CA VA
rs28933389 12244C>T, 165548010G>A, 72043156G>A, 812C>T, BCHE: Fluoride resistant I, BCHE:Thr243Met, Thr271Met
G > A
Missense
Thr271Met
No VIP available CA VA
rs28933390 1253G>T, 12685G>T, 165547569C>A, 72042715C>A, BCHE: Fluoride resistant II, BCHE:Gly390Val, Gly418Val
C > A
Missense
Gly418Val
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  None
Alternate Symbols:  E1
PharmGKB Accession Id: PA25294

Details

Cytogenetic Location: chr3 : q26.1 - q26.2
GP mRNA Boundary: chr3 : 165490692 - 165555253
GP Gene Boundary: chr3 : 165487692 - 165565253
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.

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Irinotecan Pathway, Pharmacodynamics
    Model non-tissue specific cancer cell displaying genes which may be involved in the irinotecan pathway.
  1. Irinotecan Pathway, Pharmacokinetics
    Model human liver cell showing blood, bile and intestinal compartments, indicating tissue specific involvement of genes in the irinotecan pathway.

External Pathways

Links to non-PharmGKB pathways.

  1. Neurotransmitter Clearance In The Synaptic Cleft - (Reactome via Pathway Interaction Database)
No related genes are available

Curated Information ?

Curated Information ?

Evidence Disease
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
postanesthesia apnea

Publications related to BCHE: 20

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Concordance of butyrylcholinesterase phenotype with genotype: implications for biochemical reporting. American journal of clinical pathology. 2011. Parnas M Laura, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Butyrylcholinesterase gene mutations in patients with prolonged apnea after succinylcholine for electroconvulsive therapy. Acta anaesthesiologica Scandinavica. 2011. Mollerup H M, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Biochemical and genetic analysis of butyrylcholinesterase (BChE) in a family, due to prolonged neuromuscular blockade after the use of succinylcholine. Genetics and molecular biology. 2011. Garcia Daniel Fantozzi, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Prolonged apnea during electroconvulsive therapy in monozygotic twins: case reports. Annals of general psychiatry. 2011. Zavorotnyy Maxim, 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
Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease. The pharmacogenomics journal. 2010. Patterson C E, 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
Single nucleotide polymorphism in ABCG2 is associated with irinotecan-induced severe myelosuppression. Journal of human genetics. 2009. Cha Pei-Chieng, 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
Progression from mild cognitive impairment to Alzheimer's disease: effects of sex, butyrylcholinesterase genotype, and rivastigmine treatment. Pharmacogenetics and genomics. 2009. Ferris Steven, 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
Synergistic effect of apolipoprotein E epsilon4 and butyrylcholinesterase K-variant on progression from mild cognitive impairment to Alzheimer's disease. Pharmacogenetics and genomics. 2008. Lane Roger, 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
Five new naturally occurring mutations of the BCHE gene and frequencies of 12 butyrylcholinesterase alleles in a Brazilian population. Pharmacogenetics and genomics. 2008. Mikami Liya R, 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
Pharmacokinetics and pharmacodynamics of the novel daily rivastigmine transdermal patch compared with twice-daily capsules in Alzheimer's disease patients. Clinical pharmacology and therapeutics. 2008. Lefèvre G, 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
Two novel mutations in the BCHE gene in patients with prolonged duration of action of mivacurium or succinylcholine during anaesthesia. Pharmacogenetics and genomics. 2007. Gätke Mona R, 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
A genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch population. American journal of human genetics. 2007. Liu Fan, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Genotyping the butyrylcholinesterase in patients with prolonged neuromuscular block after succinylcholine. Anesthesiology. 2005. Levano Soledad, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Frequency of butyrylcholinesterase gene mutations in individuals with abnormal inhibition numbers: an Italian-population study. Pharmacogenetics. 2003. Lando Giuliana, 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
Regulation of attention and response to therapy in dementia by butyrylcholinesterase. Pharmacogenetics. 2003. O'Brien Kirsty K, 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
Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. CNS drug reviews. 2002. Lilienfeld Sean. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The anticancer prodrug CPT-11 is a potent inhibitor of acetylcholinesterase but is rapidly catalyzed to SN-38 by butyrylcholinesterase. Cancer research. 1999. Morton C L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Identification of two different point mutations associated with the fluoride-resistant phenotype for human butyrylcholinesterase. American journal of human genetics. 1992. Nogueira C P, 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
Genetic variants of human serum cholinesterase influence metabolism of the muscle relaxant succinylcholine. Pharmacology & therapeutics. 1990. Lockridge O. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase. Proceedings of the National Academy of Sciences of the United States of America. 1989. McGuire M C, et al. PubMed

LinkOuts

Entrez Gene:
590
OMIM:
177400
UCSC Genome Browser:
NM_000055
RefSeq RNA:
NM_000055
RefSeq Protein:
NP_000046
RefSeq DNA:
AC_000046
AC_000135
NC_000003
NG_009031
NT_005612
NW_001838884
NW_921807
UniProtKB:
CHLE_HUMAN (P06276)
Ensembl:
ENSG00000114200
GenAtlas:
BCHE
GeneCard:
BCHE
MutDB:
BCHE
ALFRED:
LO011426O
HuGE:
BCHE
Comparative Toxicogenomics Database:
590
ModBase:
P06276
HumanCyc Gene:
HS03747
HGNC:
983

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