Evans, David M; Spencer, Chris CA; Pointon, Jennifer J; Su, Zhan; Harvey, David; Kochan, Grazyna; Oppermann, Udo; Dilthey, Alexander; Pirinen, Matti; Stone, Millicent A; +86 more... Appleton, Louise; Moutsianas, Loukas; Leslie, Stephen; Wordsworth, Tom; Kenna, Tony J; Karaderi, Tugce; Thomas, Gethin P; Ward, Michael M; Weisman, Michael H; Farrar, Claire; Bradbury, Linda A; Danoy, Patrick; Inman, Robert D; Maksymowych, Walter; Gladman, Dafna; Rahman, Proton; Spondyloarthritis Research Consortium of Canada (SPARCC); Morgan, Ann; Marzo-Ortega, Helena; Bowness, Paul; Gaffney, Karl; Gaston, JS Hill; Smith, Malcolm; Bruges-Armas, Jacome; Couto, Ana-Rita; Sorrentino, Rosa; Paladini, Fabiana; Ferreira, Manuel A; Xu, Huji; Liu, Yu; Jiang, Lei; Lopez-Larrea, Carlos; Díaz-Peña, Roberto; López-Vázquez, Antonio; Zayats, Tetyana; Band, Gavin; Bellenguez, Céline; Blackburn, Hannah; Blackwell, Jenefer M; Bramon, Elvira; Bumpstead, Suzannah J; Casas, Juan P; Corvin, Aiden; Craddock, Nicholas; Deloukas, Panos; Dronov, Serge; Duncanson, Audrey; Edkins, Sarah; Freeman, Colin; Gillman, Matthew; Gray, Emma; Gwilliam, Rhian; Hammond, Naomi; Hunt, Sarah E; Jankowski, Janusz; Jayakumar, Alagurevathi; Langford, Cordelia; Liddle, Jennifer; Markus, Hugh S; Mathew, Christopher G; McCann, Owen T; McCarthy, Mark I; Palmer, Colin NA; Peltonen, Leena; Plomin, Robert; Potter, Simon C; Rautanen, Anna; Ravindrarajah, Radhi; Ricketts, Michelle; Samani, Nilesh; Sawcer, Stephen J; Strange, Amy; Trembath, Richard C; Viswanathan, Ananth C; Waller, Matthew; Weston, Paul; Whittaker, Pamela; Widaa, Sara; Wood, Nicholas W; McVean, Gilean; Reveille, John D; Wordsworth, B Paul; Brown, Matthew A; Donnelly, Peter; Australo-Anglo-American Spondyloarthritis Consortium (TASC); Wellcome Trust Case Control Consortium 2 (WTCCC2); (2011) Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nature genetics, 43 (8). pp. 761-767. ISSN 1061-4036 DOI: https://doi.org/10.1038/ng.873
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Abstract
Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.
| Item Type | Article |
|---|---|
| Keywords | genome-wide association, inflammatory-bowel-disease, genetic, association, trims precursors, aminopeptidase, risk, hla, population, promotes, cells |
| Faculty and Department | Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology |
| Research Centre | Centre for Global Non-Communicable Diseases (NCDs) |
| PubMed ID | 21743469 |
| ISI | 293178300012 |
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