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Anesth Analg 2008; 106:147-151
© 2008 International Anesthesia Research Society
doi: 10.1213/01.ane.0000296455.31211.bd
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TECHNICAL COMMUNICATION

Rapid and Accurate Detection of Atypical– and Kalow–Variants in the Butyrylcholinesterase Gene Using Denaturing High–Performance Liquid Chromatography

Soledad Levano, PhD*, Dagmar Keller, MD{dagger}, Elektra Schobinger, MD*, Albert Urwyler, MD*, and Thierry Girard, MD*

From the *Departments of Anesthesia and Research; and {dagger}Cardiology Department and Cardiology Research Group, University of Basel, Basel, Switzerland.

Address correspondence and reprint requests to Soledad Levano, PhD, Departments of Anesthesia and Research, University Hospital, 4031 Basel, Switzerland. Address e-mail to s.levano{at}unibas.ch.

BACKGROUND: Variations in the butyrylcholinesterase (BCHE) gene can prolong neuromuscular block after the administration of the neuromuscular blocking drugs succinylcholine and mivacurium. The most frequent variations in the BCHE gene are the atypical (A) and Kalow (K) variants. We, therefore, developed a detection approach for these most common variants based on the method of denaturing high-performance liquid chromatography (dHPLC).

METHODS: Forty-six subjects were included. Sixteen were known to carry either the normal sequence or different combinations of A- and K-variants and 30 test subjects were randomly selected from the general population. Three samples of the 16 were used to establish the dHPLC protocols. Results from dHPLC were blindly compared with the automated sequencing data.

RESULTS: All A- and K-variants in their heterozygous and homozygous forms were unequivocally identified by dHPLC. For all 86 tested alleles, dHPLC results were 100% concordant with DNA sequencing results. Additional genetic variations were also detected, which included G344A encoding for the silent variant (S) and a known polymorphism, A1914G.

CONCLUSIONS: The described dHPLC protocols offer a rapid and accurate screening method for the most common variants of BCHE. This screening tool might be useful in pharmacokinetic studies investigating drugs metabolized by BCHE, such as mivacurium and succinylcholine.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2008 by the International Anesthesia Research Society.