ERAP2 is associated with ankylosing spondylitis in HLA-B27-positive and HLA-B27-negative patients
Philip C Robinson, Mary-Ellen Costello, Paul Leo, Linda A Bradbury, Kelly Hollis, Adrian Cortes, Seunghun Lee, Kyung Bin Joo, Seung-Cheol Shim, Michael Weisman, Michael Ward, Xiaodong Zhou, Henri-Jean Garchon, Gilles Chiocchia, Johannes Nossent, Benedicte A Lie, Øystein Førre, Jaakko Tuomilehto, Kari Laiho, Lei Jiang, Yu Liu, Xin Wu, Dirk Elewaut, Ruben Burgos-Vargas, Lianne S Gensler, Simon Stebbings, Nigil Haroon, Juan Mulero, Jose Luis Fernandez-Sueiro, Miguel A Gonzalez-Gay, Carlos Lopez-Larrea, Paul Bowness, Karl Gafney, John S Hill Gaston, Dafna D Gladman, Proton Rahman, Walter P Maksymowych, Huji Xu, Irene E van der Horst-Bruinsma, Chung-Tei Chou, Raphael Valle-Oñate, María Consuelo Romero-Sánchez, Inger Myrnes Hansen, Fernando M Pimentel-Santos, Robert D Inman, Javier Martin, Maxime Breban, David Evans, John D Reveille, Tae-Hwan Kim, B Paul Wordsworth, Matthew A Brown
Published Online First 27 April 2015
The association of endoplasmic reticulum aminopeptidase 2 (ERAP2) with ankylosing spondylitis (AS) was recently described in the large International Genetics of AS Consortium Immunochip study.1 Variants in ERAP2 have also been associated with inflammatory bowel disease, psoriasis, acute anterior uveitis and birdshot chorioretinopathy.2–5 Subsequent investigation demonstrated an association of ERAP2 with AS which was present when one conditioned on one of the two independent haplotypes of ERAP1 associated with AS or when HLA-B27-negative patients were analysed separately.1 These two analyses provide analogous evidence for the association of ERAP2 with AS in HLA-B27-negative cases because of the genetic interaction between HLA-B27 and the AS-associated ERAP1 variants in AS cases. ERAP1 and ERAP2 are located on chromosome 5q15 in the opposite orientation. The locus is challenging to analyse because of the strong linkage disequilibrium (LD) across the locus and the epistasis between ERAP1 and HLA-B alleles associated with AS. We therefore sought to investigate the association of ERAP2 with AS in HLA-B27-positive patients.6 This is of clinical importance because functional studies … (full text available by payment...)
The great and the good lined up...! Would be good if the test was easily available. Oh well. Sigh.