Five new naturally occurring mutations of the BCHE gene and frequencies of 12 butyrylcholinesterase alleles in a Brazilian population

Liya R. Mikami, Stacy Wieseler, Ricardo L.R. Souza, Lawrence M. Schopfer, Florian Nachon, Oksana Lockridge, Eleidi A. Chautard-Freire-Maia

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Human butyrylcholinesterase (BChE; EC 3.1.1.8) is codified by the BCHE gene (3q26.1-q26.2) in which 65 variants have been identified. BChE is a scavenger of organophosphorus and carbamate compounds and hydrolyzes succinylcholine, mivacurium and cocaine. The present study describes 12 naturally occurring BCHE mutations including five new mutations (K12R, G15G, V294M, G333C and R470W) identified in 366 blood donors from Southern Brazil. Exons 2 and 4 of the BCHE gene were examined by PCR-SSCA and samples with unexpected electrophoretic patterns were sequenced. The respective nucleotide substitution that characterizes each of the four new nonsynonymous mutations was introduced into BCHE cDNA by site directed mutagenesis and transfected into human embryonic kidney 293T cells and/or Chinese hamster ovary cells. The catalyzed hydrolysis of butyrylthiocholine (BTC) by BChE was measured by the Ellman method. Enzyme kinetic parameters obtained after the expression of the respective recombinant BChE evaluated the effects of the four nonsynonymous mutations. Thirty-four out of 366 individuals carried a BChE mutation in exon 2. The K variant mutation, A539T in exon 4, was present in one out of three persons. Gene expression showed that only one of the newly identified mutations (G333C) altered BChE activity, leading to a decrease of about 80% in relation to the wild-type enzyme.

Original languageEnglish (US)
Pages (from-to)213-218
Number of pages6
JournalPharmacogenetics and Genomics
Volume18
Issue number3
DOIs
StatePublished - Mar 2008

Keywords

  • Apnea
  • BCHE allele frequencies
  • BCHE gene
  • Butyrylcholinesterase mutations
  • Gene expression

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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