Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleArticle

Identification of New Human CYP2C19 Alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian Poor Metabolizer of Mephenytoin

Gordon C. Ibeanu, Joyce A. Goldstein, Urs Meyer, Simone Benhamou, Christine Bouchardy, Pierre Dayer, Burhan I. Ghanayem and Joyce Blaisdell
Journal of Pharmacology and Experimental Therapeutics September 1998, 286 (3) 1490-1495;
Gordon C. Ibeanu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joyce A. Goldstein
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Urs Meyer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simone Benhamou
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christine Bouchardy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pierre Dayer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Burhan I. Ghanayem
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joyce Blaisdell
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

A genetic polymorphism in the metabolism of the anticonvulsant drugS-mephenytoin has been attributed to defectiveCYP2C19 alleles. This genetic polymorphism displays large interracial differences with the poor metabolizer (PM) phenotype representing 2–5% of Caucasian and 13–23% of Oriental populations. In the present study, we identified two new mutations inCYP2C19 in a single Swiss Caucasian PM outlier (JOB 1) whose apparent genotype (CYP2C19*1/CYP2C19*2) did not agree with his PM phenotype. These mutations consisted of a single base pair mutation (G395A) in exon 3 resulting in an Arg132→Gln coding change and a (G276C) mutation in exon 2 resulting in a coding change Glu92→Asp. However, the G276C mutation and the G395A mutation resided on separate alleles. Genotyping tests of a family study of JOB1 showed that the exon 2 change occurred on the CYP2C19*2 allele, which also contained the known splice mutation in exon 5 (this variant is termedCYP2C19*2B to distinguish it from the original splice variant now termed CYP2C19*2A). The exon 3 mutation resided on a separate allele (termed CYP2C19*6). In all other respects this allele was identical to one of two wild-type alleles, CYP2C19*1B. The incidence ofCYP2C19*6 in a European Caucasian population phenotyped for mephenytoin metabolism was 0/344 (99% confidence limits of 0 to 0.9%). Seven of 46 Caucasian CYP2C19*2 alleles wereCYP2C19*2B(15%) and 85% wereCYP2C19*2A. The Arg132Gln mutation was produced by site-directed mutatgenesis and the recombinant protein expressed in a bacterial cDNA expression system. Recombinant CYP2C19 6 had negligible catalytic activity toward S-mephenytoin compared with CYP2C19 1B, which is consistent with the conclusion thatCYP2C19*6 represents a PM allele. Thus, the newCYP2C19*6 allele contributes to the PM phenotype in Caucasians.

Footnotes

  • Send reprint requests to: Joyce Blaisdell (C3–01), NIEHS, P.O. Box 12233, Room C324, 111 Alexander Drive, Research Triangle Park, NC 27709. E-mail: Blaisde1{at}NIEHS.NIH.GOV

  • ↵1 This work was supported in part (S.M., C.B., P.D.) by the Swiss Cancer League, Switzerland (FOR063); League against Cancer of Fribourg, Switzerland (FOR381.88); Cancer Research, Switzerland (AKT617); and Fund for Clinical Research against Cancer, Gustave-Roussy Institute, Villejuif, France (88D28).

  • Abbreviations:
    PM
    poor metabolizer
    EM
    extensive metabolizer
    PCR
    polymerase chain reaction
    HI
    hydroxylation index
    CYP
    cytochrome P450
    RFLP
    restriction fragment length polymorphism
    • Received February 13, 1998.
    • Accepted May 6, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics
Vol. 286, Issue 3
1 Sep 1998
  • Table of Contents
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Identification of New Human CYP2C19 Alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian Poor Metabolizer of Mephenytoin
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Identification of New Human CYP2C19 Alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian Poor Metabolizer of Mephenytoin

Gordon C. Ibeanu, Joyce A. Goldstein, Urs Meyer, Simone Benhamou, Christine Bouchardy, Pierre Dayer, Burhan I. Ghanayem and Joyce Blaisdell
Journal of Pharmacology and Experimental Therapeutics September 1, 1998, 286 (3) 1490-1495;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleArticle

Identification of New Human CYP2C19 Alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian Poor Metabolizer of Mephenytoin

Gordon C. Ibeanu, Joyce A. Goldstein, Urs Meyer, Simone Benhamou, Christine Bouchardy, Pierre Dayer, Burhan I. Ghanayem and Joyce Blaisdell
Journal of Pharmacology and Experimental Therapeutics September 1, 1998, 286 (3) 1490-1495;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • CRV431 Decreases Liver Fibrosis and Tumor Development
  • Evidence That Melanocortin 4 Receptor Mediates Hemorrhagic Shock Reversal Caused by Melanocortin Peptides
  • Antagonism of Immunostimulatory CpG-Oligodeoxynucleotides by 4-Aminoquinolines and Other Weak Bases: Mechanistic Studies
Show more Article

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics