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

, Spondyloarthritis Research Consortium of Canada (SPARCC) (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

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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
Uncontrolled Keywords: genetics,genetics,metabolism,case-control studies,genetics,disease susceptibility,european continental ancestry group,genome-wide association study,genetics,humans,genetics,genetics,genetics,meta-analysis as topic,minor histocompatibility antigens,metabolism,genetics,receptors, peptide,genetics,genetics,genetics
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: LivePure Connector
Date Deposited: 26 Aug 2020 00:01
Last Modified: 30 Aug 2020 23:51
URI: https://ueaeprints.uea.ac.uk/id/eprint/76609
DOI: 10.1038/ng.873

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