Expression of three naturally occurring genetic variants (G75R, E90D, I99M) of the BCHE gene of human butyrylcholinesterase

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The present paper examined the effects of three non synonymous BCHE mutations (G75R, E90D and /99M) on enzyme kinetic parameters obtained after the expression of the respective recombinant BChEs. The respective nucleotide substitution that characterizes each of the three variants was introduced into BCHE cDNA by site directed mutagenesis and transfected into human embryonic kidney 293 T cells and Chinese hamster ovary cells (for E90D). BChE catalysed hydrolysis of butyrylthiocoline (BTC) was measured by Ellman method. The expression results showed that: (1) the activity of the G75R enzyme represents approximately 45% of the wild-type activity, whereas that of the I99M enzyme does not differ from the wild-type; (2) the E90D enzyme presents a silent phenotype; disruption of the salt bridge between E90 and R42 may cause the enzyme to be rapidly degraded inside the cells. In homozygous form the E90D enzyme may confer increased susceptibility to succinylcholine, but may delay cognitive impairment in aged individuals. BChE genotyping may become important for estimating prognosis, and the knowledge of the genetic variants of BChE in a particular population may be useful for carrying out the genotyping assays

Original languageEnglish (US)
Pages (from-to)681-685
Number of pages5
JournalPharmacogenetics and Genomics
Volume17
Issue number9
DOIs
StatePublished - Sep 1 2007

Fingerprint

Butyrylcholinesterase
Enzymes
Genes
Succinylcholine
Site-Directed Mutagenesis
Cricetulus
Ovary
Hydrolysis
Nucleotides
Complementary DNA
Salts
T-Lymphocytes
Phenotype
Kidney
Population

Keywords

  • Apnea
  • BCHE gene
  • Butyrylcholinesterase mutations
  • Gene expression

ASJC Scopus subject areas

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

Cite this

Expression of three naturally occurring genetic variants (G75R, E90D, I99M) of the BCHE gene of human butyrylcholinesterase. / Mikami, Liya R.; Wieseler, Stacy; Souza, Ricardo L R; Schopfer, Lawrence M; Lockridge, Oksana; Chautard-Freire-Maia, Eleidi A.

In: Pharmacogenetics and Genomics, Vol. 17, No. 9, 01.09.2007, p. 681-685.

Research output: Contribution to journalArticle

Mikami, Liya R. ; Wieseler, Stacy ; Souza, Ricardo L R ; Schopfer, Lawrence M ; Lockridge, Oksana ; Chautard-Freire-Maia, Eleidi A. / Expression of three naturally occurring genetic variants (G75R, E90D, I99M) of the BCHE gene of human butyrylcholinesterase. In: Pharmacogenetics and Genomics. 2007 ; Vol. 17, No. 9. pp. 681-685.
@article{eba7001b482347da93ac8f1ec01ad8a1,
title = "Expression of three naturally occurring genetic variants (G75R, E90D, I99M) of the BCHE gene of human butyrylcholinesterase",
abstract = "The present paper examined the effects of three non synonymous BCHE mutations (G75R, E90D and /99M) on enzyme kinetic parameters obtained after the expression of the respective recombinant BChEs. The respective nucleotide substitution that characterizes each of the three variants was introduced into BCHE cDNA by site directed mutagenesis and transfected into human embryonic kidney 293 T cells and Chinese hamster ovary cells (for E90D). BChE catalysed hydrolysis of butyrylthiocoline (BTC) was measured by Ellman method. The expression results showed that: (1) the activity of the G75R enzyme represents approximately 45{\%} of the wild-type activity, whereas that of the I99M enzyme does not differ from the wild-type; (2) the E90D enzyme presents a silent phenotype; disruption of the salt bridge between E90 and R42 may cause the enzyme to be rapidly degraded inside the cells. In homozygous form the E90D enzyme may confer increased susceptibility to succinylcholine, but may delay cognitive impairment in aged individuals. BChE genotyping may become important for estimating prognosis, and the knowledge of the genetic variants of BChE in a particular population may be useful for carrying out the genotyping assays",
keywords = "Apnea, BCHE gene, Butyrylcholinesterase mutations, Gene expression",
author = "Mikami, {Liya R.} and Stacy Wieseler and Souza, {Ricardo L R} and Schopfer, {Lawrence M} and Oksana Lockridge and Chautard-Freire-Maia, {Eleidi A.}",
year = "2007",
month = "9",
day = "1",
doi = "10.1097/01.fpc.0000236333.49422.86",
language = "English (US)",
volume = "17",
pages = "681--685",
journal = "Pharmacogenetics and Genomics",
issn = "1744-6872",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

TY - JOUR

T1 - Expression of three naturally occurring genetic variants (G75R, E90D, I99M) of the BCHE gene of human butyrylcholinesterase

AU - Mikami, Liya R.

AU - Wieseler, Stacy

AU - Souza, Ricardo L R

AU - Schopfer, Lawrence M

AU - Lockridge, Oksana

AU - Chautard-Freire-Maia, Eleidi A.

PY - 2007/9/1

Y1 - 2007/9/1

N2 - The present paper examined the effects of three non synonymous BCHE mutations (G75R, E90D and /99M) on enzyme kinetic parameters obtained after the expression of the respective recombinant BChEs. The respective nucleotide substitution that characterizes each of the three variants was introduced into BCHE cDNA by site directed mutagenesis and transfected into human embryonic kidney 293 T cells and Chinese hamster ovary cells (for E90D). BChE catalysed hydrolysis of butyrylthiocoline (BTC) was measured by Ellman method. The expression results showed that: (1) the activity of the G75R enzyme represents approximately 45% of the wild-type activity, whereas that of the I99M enzyme does not differ from the wild-type; (2) the E90D enzyme presents a silent phenotype; disruption of the salt bridge between E90 and R42 may cause the enzyme to be rapidly degraded inside the cells. In homozygous form the E90D enzyme may confer increased susceptibility to succinylcholine, but may delay cognitive impairment in aged individuals. BChE genotyping may become important for estimating prognosis, and the knowledge of the genetic variants of BChE in a particular population may be useful for carrying out the genotyping assays

AB - The present paper examined the effects of three non synonymous BCHE mutations (G75R, E90D and /99M) on enzyme kinetic parameters obtained after the expression of the respective recombinant BChEs. The respective nucleotide substitution that characterizes each of the three variants was introduced into BCHE cDNA by site directed mutagenesis and transfected into human embryonic kidney 293 T cells and Chinese hamster ovary cells (for E90D). BChE catalysed hydrolysis of butyrylthiocoline (BTC) was measured by Ellman method. The expression results showed that: (1) the activity of the G75R enzyme represents approximately 45% of the wild-type activity, whereas that of the I99M enzyme does not differ from the wild-type; (2) the E90D enzyme presents a silent phenotype; disruption of the salt bridge between E90 and R42 may cause the enzyme to be rapidly degraded inside the cells. In homozygous form the E90D enzyme may confer increased susceptibility to succinylcholine, but may delay cognitive impairment in aged individuals. BChE genotyping may become important for estimating prognosis, and the knowledge of the genetic variants of BChE in a particular population may be useful for carrying out the genotyping assays

KW - Apnea

KW - BCHE gene

KW - Butyrylcholinesterase mutations

KW - Gene expression

UR - http://www.scopus.com/inward/record.url?scp=34547914796&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547914796&partnerID=8YFLogxK

U2 - 10.1097/01.fpc.0000236333.49422.86

DO - 10.1097/01.fpc.0000236333.49422.86

M3 - Article

C2 - 17700357

AN - SCOPUS:34547914796

VL - 17

SP - 681

EP - 685

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

SN - 1744-6872

IS - 9

ER -