Investigating the genetic association between ERAP1 and ankylosing spondylitis

Harvey, David, Pointon, Jennifer J., Evans, David M., Karaderi, Tugce, Farrar, Claire, Appleton, Louise H., Sturrock, Roger D., Stone, Millicent A., Oppermann, Udo, Brown, Matthew A. and Wordsworth, B. Paul (2009) Investigating the genetic association between ERAP1 and ankylosing spondylitis. Human Molecular Genetics, 18 21: 4204-4212. doi:10.1093/hmg/ddp371

Author Harvey, David
Pointon, Jennifer J.
Evans, David M.
Karaderi, Tugce
Farrar, Claire
Appleton, Louise H.
Sturrock, Roger D.
Stone, Millicent A.
Oppermann, Udo
Brown, Matthew A.
Wordsworth, B. Paul
Title Investigating the genetic association between ERAP1 and ankylosing spondylitis
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2009-11
Year available 2009
Sub-type Article (original research)
DOI 10.1093/hmg/ddp371
Volume 18
Issue 21
Start page 4204
End page 4212
Total pages 9
Place of publication Oxford, England
Publisher Oxford University Pres
Collection year 2010
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
970111 Expanding Knowledge in the Medical and Health Sciences
920116 Skeletal System and Disorders (incl. Arthritis)
920108 Immune System and Allergy
060405 Gene Expression (incl. Microarray and other genome-wide approaches)
1107 Immunology
Abstract 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.
Keyword Tumor-necrosis-factor
Extracellular TNFR1 Release
Class-i Molecules
Antigen Presentation
ER Aminopeptidase
Trims Precursors
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
UQ Diamantina Institute Publications
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Created: Wed, 07 Apr 2010, 13:31:54 EST by Kylie Hengst on behalf of UQ Diamantina Institute