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Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1
Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,64...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Pub. Group
2015
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443427/ https://www.ncbi.nlm.nih.gov/pubmed/25994336 http://dx.doi.org/10.1038/ncomms8146 |
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| author | Cortes, Adrian Pulit, Sara L. Leo, Paul J. Pointon, Jenny J. Robinson, Philip C. Weisman, Michael H. Ward, Michael Gensler, Lianne S. Zhou, Xiaodong Garchon, Henri-Jean Chiocchia, Gilles Nossent, Johannes Lie, Benedicte A. Førre, Øystein Tuomilehto, Jaakko Laiho, Kari Bradbury, Linda A. Elewaut, Dirk Burgos-Vargas, Ruben Stebbings, Simon Appleton, Louise Farrah, Claire Lau, Jonathan Haroon, Nigil Mulero, Juan Blanco, Francisco J. Gonzalez-Gay, Miguel A. Lopez-Larrea, C Bowness, Paul Gaffney, Karl Gaston, Hill Gladman, Dafna D. Rahman, Proton Maksymowych, Walter P. Crusius, J. Bart A. van der Horst-Bruinsma, Irene E. Valle-Oñate, Raphael Romero-Sánchez, Consuelo Hansen, Inger Myrnes Pimentel-Santos, Fernando M. Inman, Robert D. Martin, Javier Breban, Maxime Wordsworth, Bryan Paul Reveille, John D. Evans, David M. de Bakker, Paul I.W. Brown, Matthew A. |
| author_facet | Cortes, Adrian Pulit, Sara L. Leo, Paul J. Pointon, Jenny J. Robinson, Philip C. Weisman, Michael H. Ward, Michael Gensler, Lianne S. Zhou, Xiaodong Garchon, Henri-Jean Chiocchia, Gilles Nossent, Johannes Lie, Benedicte A. Førre, Øystein Tuomilehto, Jaakko Laiho, Kari Bradbury, Linda A. Elewaut, Dirk Burgos-Vargas, Ruben Stebbings, Simon Appleton, Louise Farrah, Claire Lau, Jonathan Haroon, Nigil Mulero, Juan Blanco, Francisco J. Gonzalez-Gay, Miguel A. Lopez-Larrea, C Bowness, Paul Gaffney, Karl Gaston, Hill Gladman, Dafna D. Rahman, Proton Maksymowych, Walter P. Crusius, J. Bart A. van der Horst-Bruinsma, Irene E. Valle-Oñate, Raphael Romero-Sánchez, Consuelo Hansen, Inger Myrnes Pimentel-Santos, Fernando M. Inman, Robert D. Martin, Javier Breban, Maxime Wordsworth, Bryan Paul Reveille, John D. Evans, David M. de Bakker, Paul I.W. Brown, Matthew A. |
| author_sort | Cortes, Adrian |
| collection | PubMed |
| description | Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype. |
| format | Online Article Text |
| id | pubmed-4443427 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2015 |
| publisher | Nature Pub. Group |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-44434272015-06-18 Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1 Cortes, Adrian Pulit, Sara L. Leo, Paul J. Pointon, Jenny J. Robinson, Philip C. Weisman, Michael H. Ward, Michael Gensler, Lianne S. Zhou, Xiaodong Garchon, Henri-Jean Chiocchia, Gilles Nossent, Johannes Lie, Benedicte A. Førre, Øystein Tuomilehto, Jaakko Laiho, Kari Bradbury, Linda A. Elewaut, Dirk Burgos-Vargas, Ruben Stebbings, Simon Appleton, Louise Farrah, Claire Lau, Jonathan Haroon, Nigil Mulero, Juan Blanco, Francisco J. Gonzalez-Gay, Miguel A. Lopez-Larrea, C Bowness, Paul Gaffney, Karl Gaston, Hill Gladman, Dafna D. Rahman, Proton Maksymowych, Walter P. Crusius, J. Bart A. van der Horst-Bruinsma, Irene E. Valle-Oñate, Raphael Romero-Sánchez, Consuelo Hansen, Inger Myrnes Pimentel-Santos, Fernando M. Inman, Robert D. Martin, Javier Breban, Maxime Wordsworth, Bryan Paul Reveille, John D. Evans, David M. de Bakker, Paul I.W. Brown, Matthew A. Nat Commun Article Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype. Nature Pub. Group 2015-05-21 /pmc/articles/PMC4443427/ /pubmed/25994336 http://dx.doi.org/10.1038/ncomms8146 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| spellingShingle | Article Cortes, Adrian Pulit, Sara L. Leo, Paul J. Pointon, Jenny J. Robinson, Philip C. Weisman, Michael H. Ward, Michael Gensler, Lianne S. Zhou, Xiaodong Garchon, Henri-Jean Chiocchia, Gilles Nossent, Johannes Lie, Benedicte A. Førre, Øystein Tuomilehto, Jaakko Laiho, Kari Bradbury, Linda A. Elewaut, Dirk Burgos-Vargas, Ruben Stebbings, Simon Appleton, Louise Farrah, Claire Lau, Jonathan Haroon, Nigil Mulero, Juan Blanco, Francisco J. Gonzalez-Gay, Miguel A. Lopez-Larrea, C Bowness, Paul Gaffney, Karl Gaston, Hill Gladman, Dafna D. Rahman, Proton Maksymowych, Walter P. Crusius, J. Bart A. van der Horst-Bruinsma, Irene E. Valle-Oñate, Raphael Romero-Sánchez, Consuelo Hansen, Inger Myrnes Pimentel-Santos, Fernando M. Inman, Robert D. Martin, Javier Breban, Maxime Wordsworth, Bryan Paul Reveille, John D. Evans, David M. de Bakker, Paul I.W. Brown, Matthew A. Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1 |
| title | Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1 |
| title_full | Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1 |
| title_fullStr | Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1 |
| title_full_unstemmed | Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1 |
| title_short | Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1 |
| title_sort | major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with erap1 |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443427/ https://www.ncbi.nlm.nih.gov/pubmed/25994336 http://dx.doi.org/10.1038/ncomms8146 |
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