Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://doi.org/10.1186/ar3309 |
Resumo: | Introduction: A number of genetic-association studies have identified genes contributing to ankylosing spondylitis (AS) susceptibility but such approaches provide little information as to the gene activity changes occurring during the disease process. Transcriptional profiling generates a 'snapshot' of the sampled cells' activity and thus can provide insights into the molecular processes driving the disease process. We undertook a whole-genome microarray approach to identify candidate genes associated with AS and validated these gene-expression changes in a larger sample cohort.Methods: A total of 18 active AS patients, classified according to the New York criteria, and 18 gender- and age-matched controls were profiled using Illumina HT-12 whole-genome expression BeadChips which carry cDNAs for 48,000 genes and transcripts. Class comparison analysis identified a number of differentially expressed candidate genes. These candidate genes were then validated in a larger cohort using qPCR-based TaqMan low density arrays (TLDAs).Results: A total of 239 probes corresponding to 221 genes were identified as being significantly different between patients and controls with a P-value <0.0005 (80% confidence level of false discovery rate). Forty-seven genes were then selected for validation studies, using the TLDAs. Thirteen of these genes were validated in the second patient cohort with 12 downregulated 1.3- to 2-fold and only 1 upregulated (1.6-fold). Among a number of identified genes with well-documented inflammatory roles we also validated genes that might be of great interest to the understanding of AS progression such as SPOCK2 (osteonectin) and EP300, which modulate cartilage and bone metabolism.Conclusions: We have validated a gene expression signature for AS from whole blood and identified strong candidate genes that may play roles in both the inflammatory and joint destruction aspects of the disease. |
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Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspectsPERIPHERAL-BLOODINTERFERON-GAMMAT-CELLSILLUMINA MICROARRAYEXPRESSION PROFILESSPONDYLOARTHROPATHYSUSCEPTIBILITYCHONDROCYTESPATHOGENESISLYMPHOCYTESImmunology and AllergyRheumatologyImmunologyIntroduction: A number of genetic-association studies have identified genes contributing to ankylosing spondylitis (AS) susceptibility but such approaches provide little information as to the gene activity changes occurring during the disease process. Transcriptional profiling generates a 'snapshot' of the sampled cells' activity and thus can provide insights into the molecular processes driving the disease process. We undertook a whole-genome microarray approach to identify candidate genes associated with AS and validated these gene-expression changes in a larger sample cohort.Methods: A total of 18 active AS patients, classified according to the New York criteria, and 18 gender- and age-matched controls were profiled using Illumina HT-12 whole-genome expression BeadChips which carry cDNAs for 48,000 genes and transcripts. Class comparison analysis identified a number of differentially expressed candidate genes. These candidate genes were then validated in a larger cohort using qPCR-based TaqMan low density arrays (TLDAs).Results: A total of 239 probes corresponding to 221 genes were identified as being significantly different between patients and controls with a P-value <0.0005 (80% confidence level of false discovery rate). Forty-seven genes were then selected for validation studies, using the TLDAs. Thirteen of these genes were validated in the second patient cohort with 12 downregulated 1.3- to 2-fold and only 1 upregulated (1.6-fold). Among a number of identified genes with well-documented inflammatory roles we also validated genes that might be of great interest to the understanding of AS progression such as SPOCK2 (osteonectin) and EP300, which modulate cartilage and bone metabolism.Conclusions: We have validated a gene expression signature for AS from whole blood and identified strong candidate genes that may play roles in both the inflammatory and joint destruction aspects of the disease.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNPimentel-Santos, FernandoLigeiro, DárioMatos, MafaldaMourão, Ana F.Costa, JoséSantos, HelenaBarcelos, AnabelaGodinho, FátimaPinto, PatriciaCruz, MargaridaFonseca, João E.Guedes-Pinto, HenriqueBranco, JaimeBrown, Matthew A.Thomas, Gethin P.2017-09-14T22:03:03Z2011-04-072011-04-07T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article8application/pdfhttps://doi.org/10.1186/ar3309eng1478-6354PURE: 3129485http://www.scopus.com/inward/record.url?scp=79953668485&partnerID=8YFLogxKhttps://doi.org/10.1186/ar3309info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:11:29Zoai:run.unl.pt:10362/23260Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:27:43.687212Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects |
title |
Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects |
spellingShingle |
Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects Pimentel-Santos, Fernando PERIPHERAL-BLOOD INTERFERON-GAMMA T-CELLS ILLUMINA MICROARRAY EXPRESSION PROFILES SPONDYLOARTHROPATHY SUSCEPTIBILITY CHONDROCYTES PATHOGENESIS LYMPHOCYTES Immunology and Allergy Rheumatology Immunology |
title_short |
Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects |
title_full |
Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects |
title_fullStr |
Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects |
title_full_unstemmed |
Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects |
title_sort |
Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects |
author |
Pimentel-Santos, Fernando |
author_facet |
Pimentel-Santos, Fernando Ligeiro, Dário Matos, Mafalda Mourão, Ana F. Costa, José Santos, Helena Barcelos, Anabela Godinho, Fátima Pinto, Patricia Cruz, Margarida Fonseca, João E. Guedes-Pinto, Henrique Branco, Jaime Brown, Matthew A. Thomas, Gethin P. |
author_role |
author |
author2 |
Ligeiro, Dário Matos, Mafalda Mourão, Ana F. Costa, José Santos, Helena Barcelos, Anabela Godinho, Fátima Pinto, Patricia Cruz, Margarida Fonseca, João E. Guedes-Pinto, Henrique Branco, Jaime Brown, Matthew A. Thomas, Gethin P. |
author2_role |
author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) RUN |
dc.contributor.author.fl_str_mv |
Pimentel-Santos, Fernando Ligeiro, Dário Matos, Mafalda Mourão, Ana F. Costa, José Santos, Helena Barcelos, Anabela Godinho, Fátima Pinto, Patricia Cruz, Margarida Fonseca, João E. Guedes-Pinto, Henrique Branco, Jaime Brown, Matthew A. Thomas, Gethin P. |
dc.subject.por.fl_str_mv |
PERIPHERAL-BLOOD INTERFERON-GAMMA T-CELLS ILLUMINA MICROARRAY EXPRESSION PROFILES SPONDYLOARTHROPATHY SUSCEPTIBILITY CHONDROCYTES PATHOGENESIS LYMPHOCYTES Immunology and Allergy Rheumatology Immunology |
topic |
PERIPHERAL-BLOOD INTERFERON-GAMMA T-CELLS ILLUMINA MICROARRAY EXPRESSION PROFILES SPONDYLOARTHROPATHY SUSCEPTIBILITY CHONDROCYTES PATHOGENESIS LYMPHOCYTES Immunology and Allergy Rheumatology Immunology |
description |
Introduction: A number of genetic-association studies have identified genes contributing to ankylosing spondylitis (AS) susceptibility but such approaches provide little information as to the gene activity changes occurring during the disease process. Transcriptional profiling generates a 'snapshot' of the sampled cells' activity and thus can provide insights into the molecular processes driving the disease process. We undertook a whole-genome microarray approach to identify candidate genes associated with AS and validated these gene-expression changes in a larger sample cohort.Methods: A total of 18 active AS patients, classified according to the New York criteria, and 18 gender- and age-matched controls were profiled using Illumina HT-12 whole-genome expression BeadChips which carry cDNAs for 48,000 genes and transcripts. Class comparison analysis identified a number of differentially expressed candidate genes. These candidate genes were then validated in a larger cohort using qPCR-based TaqMan low density arrays (TLDAs).Results: A total of 239 probes corresponding to 221 genes were identified as being significantly different between patients and controls with a P-value <0.0005 (80% confidence level of false discovery rate). Forty-seven genes were then selected for validation studies, using the TLDAs. Thirteen of these genes were validated in the second patient cohort with 12 downregulated 1.3- to 2-fold and only 1 upregulated (1.6-fold). Among a number of identified genes with well-documented inflammatory roles we also validated genes that might be of great interest to the understanding of AS progression such as SPOCK2 (osteonectin) and EP300, which modulate cartilage and bone metabolism.Conclusions: We have validated a gene expression signature for AS from whole blood and identified strong candidate genes that may play roles in both the inflammatory and joint destruction aspects of the disease. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-04-07 2011-04-07T00:00:00Z 2017-09-14T22:03:03Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://doi.org/10.1186/ar3309 |
url |
https://doi.org/10.1186/ar3309 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1478-6354 PURE: 3129485 http://www.scopus.com/inward/record.url?scp=79953668485&partnerID=8YFLogxK https://doi.org/10.1186/ar3309 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
8 application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799137904468951040 |