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

作者：Karaderi T; Keidel S M; Pointon J J; Appleton L H; Brown M A; Evans D M; Wordsworth B P^*

来源：Annals of the Rheumatic Diseases, 2014, 73(11): 2054-2058.

DOI：10.1136/annrheumdis-2014-205643

Objectives ANTXR2 variants have been associated with ankylosing spondylitis (AS) in two previous genome-wide association studies (GWAS) (p similar to 9x10(-8)). However, a genome-wide significant association (p%26lt;5x10(-8)) was not observed. We conducted a more comprehensive analysis of ANTXR2 in an independent UK sample to confirm and refine this association. %26lt;br%26gt;Methods 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. %26lt;br%26gt;Results Out of nine single nucleotide polymorphisms (SNP) in the study, five SNPs were nominally associated (p%26lt;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=6.7x10(-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. %26lt;br%26gt;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 (r(2)%26gt;= 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.

• 出版日期2014-11