Further evidence of subphenotype association with systemic lupus erythematosus susceptibility loci: a European cases only study.
<h4>Introduction</h4>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 pri...
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oai:doaj.org-article:d692975c5ef74c0bb689b2d428e6b30c2021-11-18T08:13:57ZFurther evidence of subphenotype association with systemic lupus erythematosus susceptibility loci: a European cases only study.1932-620310.1371/journal.pone.0045356https://doaj.org/article/d692975c5ef74c0bb689b2d428e6b30c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23049788/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.Elisa Alonso-PerezMarian Suarez-GestalManuel CalazaJosep Ordi-RosEva BaladaMarc BijlChryssa PapasteriadesPatricia CarreiraFotini N SkopouliTorsten WitteEmöke EndreffyMaurizio MarchiniSergio MigliaresiGian Domenico SebastianiMaria Jose SantosAna SuarezFrancisco J BlancoNadia BarizzoneRudolf PullmannSarka RuzickovaBernard R LauwerysJuan J Gomez-ReinoAntonio GonzalezEuropean Consortium of SLE DNA CollectionsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e45356 (2012) |
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Medicine R Science Q Elisa Alonso-Perez Marian Suarez-Gestal Manuel Calaza Josep Ordi-Ros Eva Balada Marc Bijl Chryssa Papasteriades Patricia Carreira Fotini N Skopouli Torsten Witte Emöke Endreffy Maurizio Marchini Sergio Migliaresi Gian Domenico Sebastiani Maria Jose Santos Ana Suarez Francisco J Blanco Nadia Barizzone Rudolf Pullmann Sarka Ruzickova Bernard R Lauwerys Juan J Gomez-Reino Antonio Gonzalez European Consortium of SLE DNA Collections Further evidence of subphenotype association with systemic lupus erythematosus susceptibility loci: a European cases only study. |
| description |
<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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. |
| format |
article |
| author |
Elisa Alonso-Perez Marian Suarez-Gestal Manuel Calaza Josep Ordi-Ros Eva Balada Marc Bijl Chryssa Papasteriades Patricia Carreira Fotini N Skopouli Torsten Witte Emöke Endreffy Maurizio Marchini Sergio Migliaresi Gian Domenico Sebastiani Maria Jose Santos Ana Suarez Francisco J Blanco Nadia Barizzone Rudolf Pullmann Sarka Ruzickova Bernard R Lauwerys Juan J Gomez-Reino Antonio Gonzalez European Consortium of SLE DNA Collections |
| author_facet |
Elisa Alonso-Perez Marian Suarez-Gestal Manuel Calaza Josep Ordi-Ros Eva Balada Marc Bijl Chryssa Papasteriades Patricia Carreira Fotini N Skopouli Torsten Witte Emöke Endreffy Maurizio Marchini Sergio Migliaresi Gian Domenico Sebastiani Maria Jose Santos Ana Suarez Francisco J Blanco Nadia Barizzone Rudolf Pullmann Sarka Ruzickova Bernard R Lauwerys Juan J Gomez-Reino Antonio Gonzalez European Consortium of SLE DNA Collections |
| author_sort |
Elisa Alonso-Perez |
| title |
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_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_sort |
further evidence of subphenotype association with systemic lupus erythematosus susceptibility loci: a european cases only study. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/d692975c5ef74c0bb689b2d428e6b30c |
| work_keys_str_mv |
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