RGD Reference Report - Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. - Rat Genome Database
Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility.
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 Morgan, A Marzo-Ortega, H Bowness, P Gaffney, K Gaston, JS Smith, M Bruges-Armas, J Couto, AR Sorrentino, R Paladini, F Ferreira, MA Xu, H Liu, Y Jiang, L Lopez-Larrea, C Diaz-Pena, R Lopez-Vazquez, 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 Donnelly, Peter Donnelly, Peter Donnelly, Peter
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 x 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 x 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.