Dataset Information

Genomewide association studies in ankylosing spondylitis

ABSTRACT: The aim of this study was to identify genes associated with ankylosing spondylitis susceptibility in British and Australian individuals of European descent.

PROVIDER: EGAS00000000104 | EGA |

REPOSITORIES: EGA

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Publications

Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility.

Evans David M DM Spencer Chris C A CC Pointon Jennifer J JJ Su Zhan Z Harvey David D Kochan Grazyna G Oppermann Udo U Dilthey Alexander A Pirinen Matti M Stone Millicent A MA Appleton Louise L Moutsianas Loukas L Leslie Stephen S Wordsworth Tom T Kenna Tony J TJ Karaderi Tugce T Thomas Gethin P GP Ward Michael M MM Weisman Michael H MH Farrar Claire C Bradbury Linda A LA Danoy Patrick P Inman Robert D RD Maksymowych Walter W Gladman Dafna D Rahman Proton P Morgan Ann A Marzo-Ortega Helena H Bowness Paul P Gaffney Karl K Gaston J S Hill JS Smith Malcolm M Bruges-Armas Jacome J Couto Ana-Rita AR Sorrentino Rosa R Paladini Fabiana F Ferreira Manuel A MA Xu Huji H Liu Yu Y Jiang Lei L Lopez-Larrea Carlos C Díaz-Peña Roberto R López-Vázquez Antonio A Zayats Tetyana T Band Gavin G Bellenguez Céline C Blackburn Hannah H Blackwell Jenefer M JM Bramon Elvira E Bumpstead Suzannah J SJ Casas Juan P JP Corvin Aiden A Craddock Nicholas N Deloukas Panos P Dronov Serge S Duncanson Audrey A Edkins Sarah S Freeman Colin C Gillman Matthew M Gray Emma E Gwilliam Rhian R Hammond Naomi N Hunt Sarah E SE Jankowski Janusz J Jayakumar Alagurevathi A Langford Cordelia C Liddle Jennifer J Markus Hugh S HS Mathew Christopher G CG McCann Owen T OT McCarthy Mark I MI Palmer Colin N A CN Peltonen Leena L Plomin Robert R Potter Simon C SC Rautanen Anna A Ravindrarajah Radhi R Ricketts Michelle M Samani Nilesh N Sawcer Stephen J SJ Strange Amy A Trembath Richard C RC Viswanathan Ananth C AC Waller Matthew M Weston Paul P Whittaker Pamela P Widaa Sara S Wood Nicholas W NW McVean Gilean G Reveille John D JD Wordsworth B Paul BP Brown Matthew A MA Donnelly Peter P

Nature genetics 20110710 8

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 ...[more]

PMID: 21743469

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Project description:We have compared synovial biopsies from ankylosing spondylitis and undifferentiated spondylitis patients with healthy controls and osteoarthritis patients Objective: In spondylarthropies, whole-genome gene expression profiling studies have been limited to peripheral blood to date. By undertaking a study in knee synovial biopsies from spondylarthropy (SpA) and ankylosing spondylitis (AS) patients we aimed to identified joint-specific candidate genes and pathways. These pathways may mediate systemic inflammation driven joint damaging processes and more specifically, the osteoproliferation that is characteristic of these conditions. Methods: RNA was extracted from six seronegative SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: 416 differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, osteoblast activity, B-cell associated, matrix catabolic, and metabolic pathways. The inflammatory mediator, MMP3, was strongly upregulated in AS/SpA samples and the Wnt pathway inhibitors DKK3 and Kremen1 were downregulated. Conclusion: Pathways mediating both systemic inflammation as well as local tissue changes were identified. This suggests initial systemic inflammation in spondylarthropies transfers to and persists in the local joint environment, subsequently mediating changes in genes directly involved in the destructive tissue remodelling. Fifteen knee synovial biopsy tissue samples consisting of six seronegative spondyloarthropy (SpA), two ankylosing spondylitis (AS), three osteoarthritis (OA) and four normal control biopsies were obtained from the Synovial Tissue Bank at the Repatriation General Hospital in Adelaide, South Australia with the appropriate ethical approval (Supplementary Table 1). All patients provided informed written consent.

Dataset Information

Genomewide association studies in ankylosing spondylitis

Publications

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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