Journal home
Advance online publication
Current issue
Archive
Press releases
Free Association (blog)
Supplements
Focuses
Guide to authors
Online submissionOnline submission
For referees
Free online issue
Contact the journal
Subscribe
Advertising
work@npg
Reprints and permissions
About this site
For librarians
 
NPG Resources
Nature
Nature Biotechnology
Nature Cell Biology
Nature Medicine
Nature Methods
Nature Reviews Cancer
Nature Reviews Genetics
Nature Reviews Molecular Cell Biology
news@nature.com
Nature Conferences
RNAi Gateway
NPG Subject areas
Biotechnology
Cancer
Chemistry
Clinical Medicine
Dentistry
Development
Drug Discovery
Earth Sciences
Evolution & Ecology
Genetics
Immunology
Materials Science
Medical Research
Microbiology
Molecular Cell Biology
Neuroscience
Pharmacology
Physics
Browse all publications
Letter
Nature Genetics  36, 471 - 475 (2004)
Published online: 11 April 2004; | doi:10.1038/ng1339

Functional variants of OCTN cation transporter genes are associated with Crohn disease

Vanya D Peltekova1, 2, Richard F Wintle3, Laurence A Rubin1, 3, 4, Christopher I Amos5, Qiqing Huang5, Xiangjun Gu5, Bill Newman1, 2, Mark Van Oene3, David Cescon1, 2, Gordon Greenberg1, Anne M Griffiths6, Peter H St George-Hyslop1, 3, 7 & Katherine A Siminovitch1, 2, 3

1  Department of Medicine, University of Toronto, University of Toronto, Toronto, Ontario, Canada, M5S 1A1.

2  Departments of Immunology and of Medical Genetics and Microbiology, University of Toronto, Mount Sinai Hospital Samuel Lunenfeld Research Institute, and Toronto General Research Institutes, Toronto, Ontario, Canada.

3  Ellipsis Biotherapeutics Corporation, 700 Bay Street, Suite 2101, Toronto, Ontario M5G 1Z6, Canada.

4  Division of Rheumatology, St. Michael's Hospital, 30 Bond St., Toronto, Ontario M5B 1W8, Canada.

5  Department of Epidemiology, University of Texas, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.

6  Department of Pediatrics, University of Toronto and The Hospital for Sick Children, Toronto, Ontario, Canada.

7  Centre for Research in Neurodegenerative Diseases, Tanz Neuroscience Building, University of Toronto, 6 Queen's Park Crescent West, Toronto, Ontario M5S 3H2, Canada, and the University Health Network, Toronto, Ontario, Canada.

Correspondence should be addressed to Katherine A Siminovitch ksimin@ellipsisbiotherapeutics.com
Crohn disease is a chronic, inflammatory disease of the gastrointestinal tract. A locus of approx250 kb at 5q31 (IBD5)1, 2 was previously associated with susceptibility to Crohn disease, as indicated by increased prevalence of a risk haplotype of 11 single-nucleotide polymorphisms3 among individuals with Crohn disease, but the pathogenic lesion in the region has not yet been identified. We report here that two variants in the organic cation transporter cluster at 5q31 (a missense substitution in SLC22A4 and a Gright arrowC transversion in the SLC22A5 promoter) form a haplotype associated with susceptibility to Crohn disease. These variants alter transcription and transporter functions of the organic cation transporters and interact with variants in another gene associated with Crohn disease, CARD15, to increase risk of Crohn disease. These results suggest that SLC22A4, SLC22A5 and CARD15 act in a common pathogenic pathway to cause Crohn disease.


MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

 Top
Abstract
Previous | Next
Table of contents
Full textFull text
Download PDFDownload PDF
Send to a friendSend to a friend

natureevents

Competing financial interests
Figures & Tables
Supplementary info
Export citation
natureproducts

Search buyers guide:

 
ADVERTISEMENT
 
Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
Journal home | Advance online publication | Current issue | Archive | Press releases | Supplements | Focuses | For authors | Online submission | Permissions | For referees | Free online issue | About the journal | Contact the journal | Subscribe | Advertising | work@npg | naturereprints | About this site | For librarians
Nature Publishing Group, publisher of Nature, and other science journals and reference works©2004 Nature Publishing Group | Privacy policy