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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Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. / Evans, David M.; Spencer, Chris C.A.; Pointon, Jennifer J.; Su, Zhan; Harvey, David; Kochan, Grazyna; Opperman, Udo; Dilthey, Alexander; Pirinen, Matti; Stone, Millicent A.; Appleton, Louise; Moutsianis, Loukas; Leslie, Stephen; Wordsworth, Tom; Kenna, Tony J.; Karaderi, Tugce; Thomas, Gethin P.; Ward, Michael M.; Weisman, Michael H.; Farrar, Claire; Bradbury, Linda A.; Danoy, Patrick; Inman, Robert D.; Maksymowych, Walter; Gladman, Dafna; Rahman, Proton; Morgan, Ann; Marzo-Ortega, Helena; Bowness, Paul; Gaffney, Karl; Gaston, J. S.Hill; Smith, Malcolm; Bruges-Armas, Jacome; Couto, Ana Rita; Sorrentino, Rosa; Paladini, Fabiana; Ferreira, Manuel A.; Xu, Huji; Liu, Yu; Jiang, Lei; Lopez-Larrea, Carlos; Díaz-Peña, Roberto; Lóepez-Vázquez, Antonio; Zayats, Tetyana; Band, Gavin; Bellenguez, Céline; Blackburn, Hannah; Blackwell, Jenefer M.; Bramon, Elvira; Bumpstead, Suzannah J.
In: Nature Genetics, Vol. 43, No. 8, 01.08.2011, p. 761-767.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility
AU - Evans, David M.
AU - Spencer, Chris C.A.
AU - Pointon, Jennifer J.
AU - Su, Zhan
AU - Harvey, David
AU - Kochan, Grazyna
AU - Opperman, Udo
AU - Dilthey, Alexander
AU - Pirinen, Matti
AU - Stone, Millicent A.
AU - Appleton, Louise
AU - Moutsianis, Loukas
AU - Leslie, Stephen
AU - Wordsworth, Tom
AU - Kenna, Tony J.
AU - Karaderi, Tugce
AU - Thomas, Gethin P.
AU - Ward, Michael M.
AU - Weisman, Michael H.
AU - Farrar, Claire
AU - Bradbury, Linda A.
AU - Danoy, Patrick
AU - Inman, Robert D.
AU - Maksymowych, Walter
AU - Gladman, Dafna
AU - Rahman, Proton
AU - Morgan, Ann
AU - Marzo-Ortega, Helena
AU - Bowness, Paul
AU - Gaffney, Karl
AU - Gaston, J. S.Hill
AU - Smith, Malcolm
AU - Bruges-Armas, Jacome
AU - Couto, Ana Rita
AU - Sorrentino, Rosa
AU - Paladini, Fabiana
AU - Ferreira, Manuel A.
AU - Xu, Huji
AU - Liu, Yu
AU - Jiang, Lei
AU - Lopez-Larrea, Carlos
AU - Díaz-Peña, Roberto
AU - Lóepez-Vázquez, Antonio
AU - Zayats, Tetyana
AU - Band, Gavin
AU - Bellenguez, Céline
AU - Blackburn, Hannah
AU - Blackwell, Jenefer M.
AU - Bramon, Elvira
AU - Bumpstead, Suzannah J.
PY - 2011/8/1
Y1 - 2011/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79960899377&partnerID=8YFLogxK
U2 - 10.1038/ng.873
DO - 10.1038/ng.873
M3 - Journal article
C2 - 21743469
AN - SCOPUS:79960899377
VL - 43
SP - 761
EP - 767
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 8
ER -
ID: 226396792