Ankylosing spondylitis is associated with the anthrax toxin receptor 2 gene (ANTXR2)

Karaderi, T., Keidel, S. M., Pointon, J. J., Appleton, L. H., Brown, M. A., Evans, D. M. and Wordsworth, B. P. (2014) Ankylosing spondylitis is associated with the anthrax toxin receptor 2 gene (ANTXR2). Annals of the Rheumatic Diseases, 73 11: 2054-2058. doi:10.1136/annrheumdis-2014-205643

Author Karaderi, T.
Keidel, S. M.
Pointon, J. J.
Appleton, L. H.
Brown, M. A.
Evans, D. M.
Wordsworth, B. P.
Title Ankylosing spondylitis is associated with the anthrax toxin receptor 2 gene (ANTXR2)
Journal name Annals of the Rheumatic Diseases   Check publisher's open access policy
ISSN 0003-4967
Publication date 2014-11-01
Year available 2014
Sub-type Article (original research)
DOI 10.1136/annrheumdis-2014-205643
Open Access Status
Volume 73
Issue 11
Start page 2054
End page 2058
Total pages 5
Place of publication London, United Kingdom
Publisher B M J Group
Collection year 2015
Language eng
Formatted abstract
Objectives ANTXR2 variants have been associated with ankylosing spondylitis (AS) in two previous genome-wide association studies (GWAS) (p∼9×10−8). However, a genome-wide significant association (p<5×10−8) was not observed. We conducted a more comprehensive analysis of ANTXR2 in an independent UK sample to confirm and refine this association.

A replication study was carried out with 2978 cases and 8365 controls. Then, these were combined with non-overlapping samples from the two previous GWAS in a meta-analysis. Human leukocyte antigen (HLA)-B27 stratification was also performed to test for ANTXR2-HLA-B27 interaction.

Results Out of nine single nucleotide polymorphisms (SNP) in the study, five SNPs were nominally associated (p<0.05) with AS in the replication dataset. In the meta-analysis, eight SNPs showed evidence of association, the strongest being with rs12504282 (OR=0.88, p=6.7×10−9). Seven of these SNPs showed evidence for association in the HLA-B27-positive subgroup, but none was associated with HLA-B27-negative AS. However, no statistically significant interaction was detected between HLA-B27 and ANTXR2 variants.

Conclusions ANTXR2 variants are clearly associated with AS. The top SNPs from two previous GWAS (rs4333130 and rs4389526) and this study (rs12504282) are in strong linkage disequilibrium (r2≥0.76). All are located near a putative regulatory region. Further studies are required to clarify the role played by these ANTXR2 variants in AS.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
UQ Diamantina Institute Publications
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