Skip Navigation


Human Molecular Genetics Advance Access originally published online on August 18, 2009
Human Molecular Genetics 2009 18(21):4204-4212; doi:10.1093/hmg/ddp371
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
18/21/4204    most recent
ddp371v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Harvey, D.
Right arrow Articles by Wordsworth, B. P.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Harvey, D.
Right arrow Articles by Wordsworth, B. P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2009 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Investigating the genetic association between ERAP1 and ankylosing spondylitis

David Harvey1, Jennifer J. Pointon1, David M. Evans2, Tugce Karaderi1, Claire Farrar1, Louise H. Appleton1, Roger D. Sturrock3, Millicent A. Stone4, Udo Oppermann5, Matthew A. Brown1,6 and B. Paul Wordsworth1,*

1 Botnar Research Centre, Institute of Musculoskeletal Science, Oxford OX37LD, UK 2 MRC Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, University of Bristol, Bristol BS8 2BN, UK 3 Centre for Rheumatic Diseases, Glasgow Royal Infirmary, Glasgow G31 2ER, UK 4 Royal National Hospital for Rheumatic Diseases, Bath BA1 1RL, UK 5 Structural Genomics Consortium, Old Road Campus Research Building, Oxford OX3 7DQ, UK 6 Diamantina Institute of Cancer, Immunology and Metabolic Medicine, University of Queensland, Brisbane, QLD 4102, Australia

* To whom correspondence should be addressed at: Botnar Research Centre, University of Oxford Institute of Musculoskeletal Science, Windmill Road, Headington, Oxford OX3 7LD, UK. Tel: +44 1865737545; Fax: +44 1865737640; Email: paul.wordsworth{at}ndm.ox.ac.uk

Received March 10, 2009; Accepted August 3, 2009

A strong association between ERAP1 and ankylosing spondylitis (AS) was recently identified by the Wellcome Trust Case Control Consortium and the Australo-Anglo-American Spondylitis Consortium (WTCCC-TASC) study. ERAP1 is highly polymorphic with strong linkage disequilibrium evident across the gene. We therefore conducted a series of experiments to try to identify the primary genetic association(s) with ERAP1. We replicated the original associations in an independent set of 730 patients and 1021 controls, resequenced ERAP1 to define the full extent of coding polymorphisms and tested all variants in additional association studies. The genetic association with ERAP1 was independently confirmed; the strongest association was with rs30187 in the replication set (P = 3.4 x 10–3). When the data were combined with the original WTCCC-TASC study the strongest association was with rs27044 (P = 1.1 x 10–9). We identified 33 sequence polymorphisms in ERAP1, including three novel and eight known non-synonymous polymorphisms. We report several new associations between AS and polymorphisms distributed across ERAP1 from the extended case–control study, the most significant of which was with rs27434 (P = 4.7 x 10–7). Regression analysis failed to identify a primary association clearly; we therefore used data from HapMap to impute genotypes for an additional 205 non-coding SNPs located within and adjacent to ERAP1. A number of highly significant associations (P < 5 x 10–9) were identified in regulatory sequences which are good candidates for causing susceptibility to AS, possibly by regulating ERAP1 expression.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.