Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • 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
  • Submit
  • 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
    • Special Sections
    • 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
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleMETABOLISM, TRANSPORT, AND PHARMACOGENOMICS

Identification and Characterization of Proximal Promoter Polymorphisms in the Human Concentrative Nucleoside Transporter 2 (SLC28A2)

Sook Wah Yee, James E. Shima, Stephanie Hesselson, Loan Nguyen, Sarah De Val, Rachel J. LaFond, Michiko Kawamoto, Susan J. Johns, Doug Stryke, Pui-Yan Kwok, Thomas E. Ferrin, Brian L. Black, David Gurwitz, Nadav Ahituv and Kathleen M. Giacomini
Journal of Pharmacology and Experimental Therapeutics March 2009, 328 (3) 699-707; DOI: https://doi.org/10.1124/jpet.108.147207
Sook Wah Yee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James E. Shima
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephanie Hesselson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Loan Nguyen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sarah De Val
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rachel J. LaFond
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michiko Kawamoto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susan J. Johns
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Doug Stryke
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pui-Yan Kwok
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas E. Ferrin
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brian L. Black
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Gurwitz
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nadav Ahituv
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathleen M. Giacomini
  • 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

The human concentrative nucleoside transporter 2 (CNT2) plays an important role in the absorption, disposition, and biological effects of endogenous nucleosides and nucleoside analog drugs. We identified genetic variation in the basal promoter region of CNT2 and characterized the function of the variants. We screened DNA from an ethnically diverse population and identified five basal promoter variants in CNT2. Three major haplotypes in the CNT2 basal promoter region were identified and were found at different allele frequencies in various ethnic groups. The common promoter variants and haplotypes were constructed and characterized for their promoter activity using luciferase reporter assays. One polymorphic variant, rs2413775 (-146T>A), with an allele frequency >20% in all populations, showed a gain of function in luciferase activity. Furthermore, in vivo mouse promoter assays of these nucleotide variants using the hydrodynamic tail vein injection, leading to their expression in the liver, demonstrated similar results. Transcription factor binding site (TFBS) analysis indicated this variant alters a hepatic nuclear factor (HNF) 1 TFBS. Electrophoretic mobility shift assay demonstrated stronger binding of HNF1α and weaker binding of HNF1β to the -146T and -146A regions, whereas the single nucleotide polymorphism (SNP), -146A, exhibited enhanced binding to both HNF1α and HNF1β, consistent with its greater activity in reporter assays. The data collectively suggest that the common variant, -146T>A, in the proximal promoter of CNT2 may result in an enhanced transcription rate of the gene and, thus, expression levels of CNT2. This SNP may play a role in variation in the pharmacokinetics and pharmacological effects of nucleoside analogs.

Footnotes

  • This work was supported in part by the National Institutes of Health National Institute of General Medical Sciences [Grant GM61390]; by the National Institutes of Health National Cancer Institute [Grant P50-CA58207]; and by the Sandler Family Supporting Foundation.

  • A grant from the New Energy and Industrial Technology Development Organization supported some of the methods of development in this study.

  • Data showing allele frequencies of CNT2 promoter variants are available at http://www.pharmgkb.org.

  • doi:10.1124/jpet.108.147207.

  • ABBREVIATIONS: CNT, concentrative nucleoside transporter; SNP, single nucleotide polymorphism; bp, base pair; HNF, hepatic nuclear factor; SOPHIE, Studies of Pharmacogenetics in Ethnically Diverse Populations; PCR, polymerase chain reaction; EMSA, electrophoretic mobility shift assay; TSS, transcription start site; LD, linkage disequilibrium.

    • Received October 8, 2008.
    • Accepted December 16, 2008.
  • 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.
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 382 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 382, Issue 2
1 Aug 2022
  • Table of Contents
  • About the Cover
  • 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 and Characterization of Proximal Promoter Polymorphisms in the Human Concentrative Nucleoside Transporter 2 (SLC28A2)
(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 ArticleMETABOLISM, TRANSPORT, AND PHARMACOGENOMICS

Identification and Characterization of Proximal Promoter Polymorphisms in the Human Concentrative Nucleoside Transporter 2 (SLC28A2)

Sook Wah Yee, James E. Shima, Stephanie Hesselson, Loan Nguyen, Sarah De Val, Rachel J. LaFond, Michiko Kawamoto, Susan J. Johns, Doug Stryke, Pui-Yan Kwok, Thomas E. Ferrin, Brian L. Black, David Gurwitz, Nadav Ahituv and Kathleen M. Giacomini
Journal of Pharmacology and Experimental Therapeutics March 1, 2009, 328 (3) 699-707; DOI: https://doi.org/10.1124/jpet.108.147207

Citation Manager Formats

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

Share
Research ArticleMETABOLISM, TRANSPORT, AND PHARMACOGENOMICS

Identification and Characterization of Proximal Promoter Polymorphisms in the Human Concentrative Nucleoside Transporter 2 (SLC28A2)

Sook Wah Yee, James E. Shima, Stephanie Hesselson, Loan Nguyen, Sarah De Val, Rachel J. LaFond, Michiko Kawamoto, Susan J. Johns, Doug Stryke, Pui-Yan Kwok, Thomas E. Ferrin, Brian L. Black, David Gurwitz, Nadav Ahituv and Kathleen M. Giacomini
Journal of Pharmacology and Experimental Therapeutics March 1, 2009, 328 (3) 699-707; DOI: https://doi.org/10.1124/jpet.108.147207
del.icio.us logo Digg logo Reddit logo Twitter 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

  • HDL Mimetic 4F Modulates Aβ Distribution in Brain and Plasma
  • AOX1 Inhibition by Gefitinib, Erlotinib, and Metabolites
  • Catalytic Activity of CYP2C9 Variants
Show more Metabolism, Transport, and Pharmacogenomics

Similar Articles

Advertisement
  • 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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics