The Identification of Butyrylcholinesterase (BCHE) Polymorphisms in a Small Australian Defence Force Cohort

Abstract

Genetic variation in the plasma enzyme butyrylcholinesterase (BCHE) affects the response of humans to xenobiotic agents. Mutations in BCHE are responsible for the majority of cases of prolonged apnea following the administration of succinylcholine. In addition, genetic variation in BCHE is linked to sensitivity to both organophosphate and carbamate compounds, including the deployment related drugs pyridostigmine, physostigmine, heptyl physostigmine and SDZ-ENZ 713. The study described in this report successfully screened the four coding regions (and surrounding intronic regions) of BCHE for both novel and known polymorphisms. High Resolution Melt (HRM) and sequencing procedures revealed 12 different genetic polymorphisms, and 35/51 individuals were shown to carry at least one BCHE polymorphism. Eight of the polymorphisms had been documented previously, two of which have been reported in individuals with succinylcholine and pyridostigmine sensitivities. Of the four novel polymorphisms found, two are predicted to change an amino acid in BCHE. This study has demonstrated clearly that unique and important functional genetic variation may be found and there may be a small subset of individuals in the ADF with enhanced sensitivity to succinylcholine and organophosphate and carbamate compounds.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2011
Accession Number
ADA538109

Entities

People

  • Justine Lewis
  • Katherine A. Shields

Organizations

  • Defence Science and Technology Group

Tags

DTIC Thesaurus Topics

  • Acetylcholinesterases
  • Amino Acids
  • Chemical Warfare
  • Chemical Warfare Agents
  • Drug Abuse
  • Genes
  • Genetic Variation
  • Genetics
  • Genotypes
  • High Resolution
  • Medical Personnel
  • Mutations
  • Nerve Agents
  • Nervous System
  • Organophosphates
  • Peripheral Nervous System
  • Pesticides

Readers

  • Molecular Genetics
  • Pavement Materials Engineering.
  • Toxicology/Environmental Toxicology

Technology Areas

  • Biotechnology