Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility.
| Title: | Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. |
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| Authors: | Evans DM; Spencer CC; Pointon JJ; Su Z; Harvey D; Kochan G; Oppermann U; Dilthey A; Pirinen M; Stone MA; Appleton L; Moutsianas L; Leslie S; Wordsworth T; Kenna TJ; Karaderi T; Thomas GP; Ward MM; Weisman MH; Farrar C; Bradbury LA; Danoy P; Inman RD; Maksymowych W; Gladman D; Rahman P; Spondyloarthritis Research Consortium of Canada; Morgan A; Marzo Ortega H; Bowness P; Gaffney K; Gaston JS; Smith M; Bruges Armas J; Couto AR; Ferreira MA; Xu H; Liu Y; Jiang L; Lopez Larrea C; Díaz Peña R; López Vázquez A; Zayats T; Band G; Bellenguez C; Blackburn H; Blackwell JM; Bramon E; Bumpstead SJ; Casas JP; Corvin A; Craddock N; Deloukas P; Dronov S; Duncanson A; Edkins S; Freeman C; Gillman M; Gray E; Gwilliam R; Hammond N; Hunt SE; Jankowski J; Jayakumar A; Langford C; Liddle J; Markus HS; Mathew CG; McCann OT; McCarthy MI; Palmer CN; Peltonen L; Plomin R; Potter SC; Rautanen A; Ravindrarajah R; Ricketts M; Samani N; Sawcer SJ; Strange A; Trembath RC; Viswanathan AC; Waller M; Weston P; Whittaker P; Widaa S; Wood NW; McVean G; Reveille JD; Wordsworth BP; Brown MA; Donnelly P; Australo Anglo American Spondyloarthritis Consortium; Wellcome Trust Case Control Consortium 2; SORRENTINO, Rosa; PALADINI, Fabiana |
| Contributors: | Evans, Dm; Spencer, Cc; Pointon, Jj; Su, Z; Harvey, D; Kochan, G; Oppermann, U; Dilthey, A; Pirinen, M; Stone, Ma; Appleton, L; Moutsianas, L; Leslie, S; Wordsworth, T; Kenna, Tj; Karaderi, T; Thomas, Gp; Ward, Mm; Weisman, Mh; Farrar, C; Bradbury, La; Danoy, P; Inman, Rd; Maksymowych, W; Gladman, D; Rahman, P; Spondyloarthritis Research Consortium of, Canada; Morgan, A; Marzo Ortega, H; Bowness, P; Gaffney, K; Gaston, J; Smith, M; Bruges Armas, J; Couto, Ar; Sorrentino, Rosa; Paladini, Fabiana; Ferreira, Ma; Xu, H; Liu, Y; Jiang, L; Lopez Larrea, C; Díaz Peña, R; López Vázquez, A; Zayats, T; Band, G; Bellenguez, C; Blackburn, H; Blackwell, Jm; Bramon, E; Bumpstead, Sj; Casas, Jp; Corvin, A; Craddock, N; Deloukas, P; Dronov, S; Duncanson, A; Edkins, S; Freeman, C; Gillman, M; Gray, E; Gwilliam, R; Hammond, N; Hunt, Se; Jankowski, J; Jayakumar, A; Langford, C; Liddle, J; Markus, H; Mathew, Cg; Mccann, Ot; Mccarthy, Mi; Palmer, Cn; Peltonen, L; Plomin, R; Potter, Sc; Rautanen, A; Ravindrarajah, R; Ricketts, M; Samani, N; Sawcer, Sj; Strange, A; Trembath, Rc; Viswanathan, Ac; Waller, M; Weston, P; Whittaker, P; Widaa, S; Wood, Nw; Mcvean, G; Reveille, Jd; Wordsworth, Bp; Brown, Ma; Donnelly, P; Australo Anglo American Spondyloarthritis, Consortium; Wellcome Trust Case Control Consortium, 2 |
| Publication Year: | 2011 |
| Collection: | Sapienza Università di Roma: CINECA IRIS |
| Subject Terms: | HLA-B27; ERAP1; ANKYLOSING SPONDYLITIS |
| Description: | 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. |
| Document Type: | article in journal/newspaper |
| File Description: | STAMPA |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/21743469; info:eu-repo/semantics/altIdentifier/wos/WOS:000293178300012; volume:43; firstpage:761; lastpage:767; numberofpages:7; journal:NATURE GENETICS; http://hdl.handle.net/11573/625165 |
| DOI: | 10.1038/ng.873 |
| Availability: | http://hdl.handle.net/11573/625165; https://doi.org/10.1038/ng.873 |
| Accession Number: | edsbas.23BF5D7E |
| Database: | BASE |