ERAP2 is associated with ankylosing spondylitis in HLA-B27-positive and HLA-B27-negative patients

Philip C Robinson¹, Mary-Ellen Costello², Paul Leo², Linda A Bradbury², Kelly Hollis², Adrian Cortes², Seunghun Lee³, Kyung Bin Joo³, Seung-Cheol Shim⁴, Michael Weisman⁵, Michael Ward⁶, Xiaodong Zhou⁷, Henri-Jean Garchon⁸, Gilles Chiocchia⁹, Johannes Nossent¹⁰, Benedicte A Lie¹¹, Øystein Førre¹², Jaakko Tuomilehto¹³, Kari Laiho¹⁴, Lei Jiang¹⁵, Yu Liu¹⁵, Xin Wu¹⁵, Dirk Elewaut¹⁶, Ruben Burgos-Vargas¹⁷, Lianne S Gensler¹⁸, Simon Stebbings¹⁹, Nigil Haroon²⁰, Juan Mulero²¹, Jose Luis Fernandez-Sueiro²², Miguel A Gonzalez-Gay²³, Carlos Lopez-Larrea²⁴, Paul Bowness²⁵, Karl Gafney²⁶, John S Hill Gaston²⁷, Dafna D Gladman²⁸, Proton Rahman²⁹, Walter P Maksymowych³⁰, Huji Xu¹⁵, Irene E van der Horst-Bruinsma³¹, Chung-Tei Chou³², Raphael Valle-Oñate³³, María Consuelo Romero-Sánchez³³, Inger Myrnes Hansen³⁴, Fernando M Pimentel-Santos³⁵, Robert D Inman²⁰, Javier Martin³⁶, Maxime Breban³⁷, David Evans³⁸, John D Reveille⁷, Tae-Hwan Kim³, B Paul Wordsworth²⁵, Matthew A Brown²

Affiliations

¹ Centre for Neurogenetics and Statistical Genomics, Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
² The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
³ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
⁴ Department of Medicine, Division of Rheumatology, Eulji University Hospital, Daejeon, Republic of Korea.
⁵ Department of Medicine/Rheumatology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁶ National Institute of Arthritis and Musculoskeletal and Skin Diseases, US National Institutes of Health, Bethesda, Maryland, USA.
⁷ Department of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, Texas, USA.
⁸ INSERM U1173, UFR Simone Veil, Versailles-Saint-Quentin University, Laboratoire d'Excellence INFLAMEX, France Genetics Division, Ambroise Paré Hospital (AP-HP), Boulogne-Billancourt, Paris, France.
⁹ INSERM U1173, UFR Simone Veil, Versailles-Saint-Quentin University, Laboratoire d'Excellence INFLAMEX, France.
¹⁰ School of Medicine, University of Western Australia, Western Australia, Perth, Australia Department of Rheumatology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
¹¹ Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway Department of Immunology, Oslo University Hospital, Oslo, Norway.
¹² Department of Rheumatology, University Hospital Oslo, Oslo, Norway.
¹³ Centre for Vascular Prevention, Danube-University Krems, Krems, Austria. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland King Abdulaziz University, Jeddah, Saudi Arabia.
¹⁴ Department of Medicine, Päijät-Häme Central Hospital, Lahti, Finland.
¹⁵ Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
¹⁶ Department of Rheumatology, Ghent University Hospital, Ghent, Belgium VIB Inflammation Research Center, Ghent, Belgium.
¹⁷ Department of Rheumatology, Faculty of Medicine, Hospital General de México, Universidad Nacional Autónoma de México, Mexico City, México.
¹⁸ University of California, San Francisco, California, USA.
¹⁹ Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
²⁰ Division of Rheumatology, Toronto Western Hospital, Toronto, Ontario, Canada.
²¹ Rheumatology Department, Hospital Puerta de Hierro, Madrid, Spain.
²² Rheumatology Department, Complejo Hospitalario La Coruña, Instituto de Investigación Biomédica A Coruña (INIBIC), La Coruña, Spain.
²³ Rheumatology Department, Hospital Marqués de Valcecilla, Instituto de Formación e Investigación Marqués de Valcecillas (IFIMAV), Santander, Spain.
²⁴ Department of Immunology, Asturias Central University Hospital, Oviedo, Spain Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
²⁵ National Institute for Health Research (NIHR) Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre, Oxford, UK.
²⁶ Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK.
²⁷ Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
²⁸ Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada Toronto Western Research Institute, Toronto, Ontario, Canada Psoriatic Arthritis Program, University Health Network, Toronto, Ontario, Canada.
²⁹ Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
³⁰ Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
³¹ Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands.
³² Department of Medicine, Division of Allergy, Immunology, Rheumatology, Taipei Veterans General Hospital, Taipei, Taiwan. School of Medicine, National Yang- Ming University, Taipei, Taiwan.
³³ SpA Group Hospital Militar, Universidad Militar Nueva Granada, Bogotá, Colombia.
³⁴ Helgelandssykehuset, Mo i Rana, Norway.
³⁵ Chronic Diseases Research Centre (CEDOC), Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.
³⁶ Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Granada, Spain.
³⁷ INSERM U1173, UFR Simone Veil, Versailles-Saint-Quentin University, Laboratoire d'Excellence INFLAMEX, France Division of Rheumatology, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt, Paris, France.
³⁸ The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia MRC Integrative Epidemiology Unit, University of Bristol, UK School of Social and Community Medicine, University of Bristol, Bristol, UK.

PMID: 25917849
PMCID: PMC4498996
DOI: 10.1136/annrheumdis-2015-207416

ERAP2 is associated with ankylosing spondylitis in HLA-B27-positive and HLA-B27-negative patients

Philip C Robinson et al. Ann Rheum Dis. 2015 Aug.

. 2015 Aug;74(8):1627-9.

doi: 10.1136/annrheumdis-2015-207416. Epub 2015 Apr 27.

Authors

Affiliations

¹ Centre for Neurogenetics and Statistical Genomics, Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
² The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
³ Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea.
⁴ Department of Medicine, Division of Rheumatology, Eulji University Hospital, Daejeon, Republic of Korea.
⁵ Department of Medicine/Rheumatology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁶ National Institute of Arthritis and Musculoskeletal and Skin Diseases, US National Institutes of Health, Bethesda, Maryland, USA.
⁷ Department of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, Texas, USA.
⁸ INSERM U1173, UFR Simone Veil, Versailles-Saint-Quentin University, Laboratoire d'Excellence INFLAMEX, France Genetics Division, Ambroise Paré Hospital (AP-HP), Boulogne-Billancourt, Paris, France.
⁹ INSERM U1173, UFR Simone Veil, Versailles-Saint-Quentin University, Laboratoire d'Excellence INFLAMEX, France.
¹⁰ School of Medicine, University of Western Australia, Western Australia, Perth, Australia Department of Rheumatology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia.
¹¹ Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway Department of Immunology, Oslo University Hospital, Oslo, Norway.
¹² Department of Rheumatology, University Hospital Oslo, Oslo, Norway.
¹³ Centre for Vascular Prevention, Danube-University Krems, Krems, Austria. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland King Abdulaziz University, Jeddah, Saudi Arabia.
¹⁴ Department of Medicine, Päijät-Häme Central Hospital, Lahti, Finland.
¹⁵ Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
¹⁶ Department of Rheumatology, Ghent University Hospital, Ghent, Belgium VIB Inflammation Research Center, Ghent, Belgium.
¹⁷ Department of Rheumatology, Faculty of Medicine, Hospital General de México, Universidad Nacional Autónoma de México, Mexico City, México.
¹⁸ University of California, San Francisco, California, USA.
¹⁹ Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
²⁰ Division of Rheumatology, Toronto Western Hospital, Toronto, Ontario, Canada.
²¹ Rheumatology Department, Hospital Puerta de Hierro, Madrid, Spain.
²² Rheumatology Department, Complejo Hospitalario La Coruña, Instituto de Investigación Biomédica A Coruña (INIBIC), La Coruña, Spain.
²³ Rheumatology Department, Hospital Marqués de Valcecilla, Instituto de Formación e Investigación Marqués de Valcecillas (IFIMAV), Santander, Spain.
²⁴ Department of Immunology, Asturias Central University Hospital, Oviedo, Spain Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain.
²⁵ National Institute for Health Research (NIHR) Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre, Oxford, UK.
²⁶ Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich, UK.
²⁷ Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
²⁸ Division of Rheumatology, University of Toronto, Toronto, Ontario, Canada Toronto Western Research Institute, Toronto, Ontario, Canada Psoriatic Arthritis Program, University Health Network, Toronto, Ontario, Canada.
²⁹ Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
³⁰ Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
³¹ Department of Rheumatology, VU University Medical Center, Amsterdam, The Netherlands.
³² Department of Medicine, Division of Allergy, Immunology, Rheumatology, Taipei Veterans General Hospital, Taipei, Taiwan. School of Medicine, National Yang- Ming University, Taipei, Taiwan.
³³ SpA Group Hospital Militar, Universidad Militar Nueva Granada, Bogotá, Colombia.
³⁴ Helgelandssykehuset, Mo i Rana, Norway.
³⁵ Chronic Diseases Research Centre (CEDOC), Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.
³⁶ Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Granada, Spain.
³⁷ INSERM U1173, UFR Simone Veil, Versailles-Saint-Quentin University, Laboratoire d'Excellence INFLAMEX, France Division of Rheumatology, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris, Boulogne-Billancourt, Paris, France.
³⁸ The University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia MRC Integrative Epidemiology Unit, University of Bristol, UK School of Social and Community Medicine, University of Bristol, Bristol, UK.

PMID: 25917849
PMCID: PMC4498996
DOI: 10.1136/annrheumdis-2015-207416

No abstract available

Keywords: Ankylosing Spondylitis; Low Back Pain; Spondyloarthritis.

PubMed Disclaimer

Conflict of interest statement

Competing interests None declared.

Figures

**Figure 1**
Local association plots of the *ERAP2* locus when the association model using *HLA-B27*-positive controls (upper) and unselected controls (lower) are used in logistic regression models that incorporate the two independent ankylosing spondylitis-associated *ERAP1* haplotypes, rs30187 and rs10050860, as covariates.

See this image and copyright information in PMC

References

1. Cortes A, Hadler J, Pointon JP, et al. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet. 2013;45:730–738. - PMC - PubMed
1. Robinson PC, Claushuis TA, Cortes A, et al. Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis. Arthritis Rheumatol. 2015;67:140–151. - PMC - PubMed
1. Tsoi LC, Spain SL, Knight J, et al. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat Genet. 2012;44:1341–1348. - PMC - PubMed
1. Franke A, McGovern DP, Barrett JC, et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat Genet. 2010;42:1118–1125. - PMC - PubMed
1. Kuiper JJ, Van Setten J, Ripke S, et al. A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy. Hum Mol Genet. 2014;23:6081–6087. - PMC - PubMed

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ERAP2 is associated with ankylosing spondylitis in HLA-B27-positive and HLA-B27-negative patients

Affiliations

ERAP2 is associated with ankylosing spondylitis in HLA-B27-positive and HLA-B27-negative patients

Authors

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Conflict of interest statement

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