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Further Evidence of Subphenotype Association with Systemic Lupus Erythematosus Susceptibility Loci: A European Cases Only Study

INTRODUCTION: Systemic Lupus Erythematosus (SLE) shows a spectrum of clinical manifestations that complicate its diagnosis, treatment and research. This variability is likely related with environmental exposures and genetic factors among which known SLE susceptibility loci are prime candidates. The...

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Autores principales: Alonso-Perez, Elisa, Suarez-Gestal, Marian, Calaza, Manuel, Ordi-Ros, Josep, Balada, Eva, Bijl, Marc, Papasteriades, Chryssa, Carreira, Patricia, Skopouli, Fotini N., Witte, Torsten, Endreffy, Emöke, Marchini, Maurizio, Migliaresi, Sergio, Sebastiani, Gian Domenico, Santos, Maria Jose, Suarez, Ana, Blanco, Francisco J., Barizzone, Nadia, Pullmann, Rudolf, Ruzickova, Sarka, Lauwerys, Bernard R., Gomez-Reino, Juan J., Gonzalez, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458859/
https://www.ncbi.nlm.nih.gov/pubmed/23049788
http://dx.doi.org/10.1371/journal.pone.0045356
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author Alonso-Perez, Elisa
Suarez-Gestal, Marian
Calaza, Manuel
Ordi-Ros, Josep
Balada, Eva
Bijl, Marc
Papasteriades, Chryssa
Carreira, Patricia
Skopouli, Fotini N.
Witte, Torsten
Endreffy, Emöke
Marchini, Maurizio
Migliaresi, Sergio
Sebastiani, Gian Domenico
Santos, Maria Jose
Suarez, Ana
Blanco, Francisco J.
Barizzone, Nadia
Pullmann, Rudolf
Ruzickova, Sarka
Lauwerys, Bernard R.
Gomez-Reino, Juan J.
Gonzalez, Antonio
author_facet Alonso-Perez, Elisa
Suarez-Gestal, Marian
Calaza, Manuel
Ordi-Ros, Josep
Balada, Eva
Bijl, Marc
Papasteriades, Chryssa
Carreira, Patricia
Skopouli, Fotini N.
Witte, Torsten
Endreffy, Emöke
Marchini, Maurizio
Migliaresi, Sergio
Sebastiani, Gian Domenico
Santos, Maria Jose
Suarez, Ana
Blanco, Francisco J.
Barizzone, Nadia
Pullmann, Rudolf
Ruzickova, Sarka
Lauwerys, Bernard R.
Gomez-Reino, Juan J.
Gonzalez, Antonio
author_sort Alonso-Perez, Elisa
collection PubMed
description INTRODUCTION: Systemic Lupus Erythematosus (SLE) shows a spectrum of clinical manifestations that complicate its diagnosis, treatment and research. This variability is likely related with environmental exposures and genetic factors among which known SLE susceptibility loci are prime candidates. The first published analyses seem to indicate that this is the case for some of them, but results are still inconclusive and we aimed to further explore this question. METHODS: European SLE patients, 1444, recruited at 17 centres from 10 countries were analyzed. Genotypes for 26 SLE associated SNPs were compared between patients with and without each of 11 clinical features: ten of the American College of Rheumatology (ACR) classification criteria (except ANAs) and age of disease onset. These analyses were adjusted for centre of recruitment, top ancestry informative markers, gender and time of follow-up. Overlap of samples with previous studies was excluded for assessing replication. RESULTS: There were three new associations: the SNPs in XKR6 and in FAM167A-BLK were associated with lupus nephritis (OR = 0.76 and 1.30, P(corr) = 0.007 and 0.03, respectively) and the SNP of MECP2, which is in chromosome X, with earlier age of disease onset in men. The previously reported association of STAT4 with early age of disease onset was replicated. Some other results were suggestive of the presence of additional associations. Together, the association signals provided support to some previous findings and to the characterization of lupus nephritis, autoantibodies and age of disease onset as the clinical features more associated with SLE loci. CONCLUSION: Some of the SLE loci shape the disease phenotype in addition to increase susceptibility to SLE. This influence is more prominent for some clinical features than for others. However, results are only partially consistent between studies and subphenotype specific GWAS are needed to unravel their genetic component.
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spelling pubmed-34588592012-10-03 Further Evidence of Subphenotype Association with Systemic Lupus Erythematosus Susceptibility Loci: A European Cases Only Study Alonso-Perez, Elisa Suarez-Gestal, Marian Calaza, Manuel Ordi-Ros, Josep Balada, Eva Bijl, Marc Papasteriades, Chryssa Carreira, Patricia Skopouli, Fotini N. Witte, Torsten Endreffy, Emöke Marchini, Maurizio Migliaresi, Sergio Sebastiani, Gian Domenico Santos, Maria Jose Suarez, Ana Blanco, Francisco J. Barizzone, Nadia Pullmann, Rudolf Ruzickova, Sarka Lauwerys, Bernard R. Gomez-Reino, Juan J. Gonzalez, Antonio PLoS One Research Article INTRODUCTION: Systemic Lupus Erythematosus (SLE) shows a spectrum of clinical manifestations that complicate its diagnosis, treatment and research. This variability is likely related with environmental exposures and genetic factors among which known SLE susceptibility loci are prime candidates. The first published analyses seem to indicate that this is the case for some of them, but results are still inconclusive and we aimed to further explore this question. METHODS: European SLE patients, 1444, recruited at 17 centres from 10 countries were analyzed. Genotypes for 26 SLE associated SNPs were compared between patients with and without each of 11 clinical features: ten of the American College of Rheumatology (ACR) classification criteria (except ANAs) and age of disease onset. These analyses were adjusted for centre of recruitment, top ancestry informative markers, gender and time of follow-up. Overlap of samples with previous studies was excluded for assessing replication. RESULTS: There were three new associations: the SNPs in XKR6 and in FAM167A-BLK were associated with lupus nephritis (OR = 0.76 and 1.30, P(corr) = 0.007 and 0.03, respectively) and the SNP of MECP2, which is in chromosome X, with earlier age of disease onset in men. The previously reported association of STAT4 with early age of disease onset was replicated. Some other results were suggestive of the presence of additional associations. Together, the association signals provided support to some previous findings and to the characterization of lupus nephritis, autoantibodies and age of disease onset as the clinical features more associated with SLE loci. CONCLUSION: Some of the SLE loci shape the disease phenotype in addition to increase susceptibility to SLE. This influence is more prominent for some clinical features than for others. However, results are only partially consistent between studies and subphenotype specific GWAS are needed to unravel their genetic component. Public Library of Science 2012-09-26 /pmc/articles/PMC3458859/ /pubmed/23049788 http://dx.doi.org/10.1371/journal.pone.0045356 Text en © 2012 Alonso-Perez et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Alonso-Perez, Elisa
Suarez-Gestal, Marian
Calaza, Manuel
Ordi-Ros, Josep
Balada, Eva
Bijl, Marc
Papasteriades, Chryssa
Carreira, Patricia
Skopouli, Fotini N.
Witte, Torsten
Endreffy, Emöke
Marchini, Maurizio
Migliaresi, Sergio
Sebastiani, Gian Domenico
Santos, Maria Jose
Suarez, Ana
Blanco, Francisco J.
Barizzone, Nadia
Pullmann, Rudolf
Ruzickova, Sarka
Lauwerys, Bernard R.
Gomez-Reino, Juan J.
Gonzalez, Antonio
Further Evidence of Subphenotype Association with Systemic Lupus Erythematosus Susceptibility Loci: A European Cases Only Study
title Further Evidence of Subphenotype Association with Systemic Lupus Erythematosus Susceptibility Loci: A European Cases Only Study
title_full Further Evidence of Subphenotype Association with Systemic Lupus Erythematosus Susceptibility Loci: A European Cases Only Study
title_fullStr Further Evidence of Subphenotype Association with Systemic Lupus Erythematosus Susceptibility Loci: A European Cases Only Study
title_full_unstemmed Further Evidence of Subphenotype Association with Systemic Lupus Erythematosus Susceptibility Loci: A European Cases Only Study
title_short Further Evidence of Subphenotype Association with Systemic Lupus Erythematosus Susceptibility Loci: A European Cases Only Study
title_sort further evidence of subphenotype association with systemic lupus erythematosus susceptibility loci: a european cases only study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458859/
https://www.ncbi.nlm.nih.gov/pubmed/23049788
http://dx.doi.org/10.1371/journal.pone.0045356
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