Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility
By David M. Evans, Chris C. A. Spencer, Jennifer J. Pointon, Z. Su, D. Harvey, G. Kochan, U. Oppermann, A. Dilthey, Matti Pirinen, M. Stone and 83 more. Nature Genetics, 2011
898 citations recorded by the source corpus.
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.
Subfields: Immunology, Rheumatology
View Paper: https://www.semanticscholar.org/paper/289deebf572693bc55a474b9e572f35e6d98d86e
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Citations in the corpus
- Major Histocompatibility Complex Genomics and Human Disease (2013, neutral): “Interaction between ERAP1 and HLAB27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility.”
- Imputing Amino Acid Polymorphisms in Human Leukocyte Antigens (2013, background): “We and others have previously demonstrated the potential of HLA imputation for a wide range of phenotypes including host control of HIV-1 replication [17,26], rheumatoid arthritis [27], ulcerative colitis [28], primary biliary cirrhosis [29], psoriasis [30], ankylosing spondylitis [31], multiple scl”
- Innate Immune Activity Conditions the Effect of Regulatory Variants upon Monocyte Gene Expression (2014, background): “The latter is tagged by peak SNPs that define a GWAS locus for inflammatory bowel disease and ankylosing spondylitis (45, 46).”