Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis
| Autor(a) principal: | |
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| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/129663 |
Resumo: | Funding Information: We thank all participants who have agreed to participate in this study. Authors also thank Mar?a Dolores Casares, ?ngeles Molina, Carmen Oloriz for the collection of Spanish samples and Hans Jurgen Hoffmann, Marianne Thomsen, Vibeke ?stergaard Thomsen, Malene Rohr Andersen, Lise Lotte B. Laursen, Helle J?rgensen, Ram Benny Christian Dessau, Niels Steen Krogh, Ulla Vogel, Paal Skytt Andersen, Ivan Brandslund, Steffen Bank, Frederik Trier M?ller, Nikolai Toft and Niels M?ller Andersen for the participation in collection and purification of Danish samples. We also thank the Danish Departments of Rheumatology for their implication in the collection of clinical data from RA patients included in the DANBIO cohort and the Danish Rheumatologic Biobank. Likewise, we would like to thank Teun van Herwaarden for steroid hormone measurements in serum samples from subjects ascertained through the HFGP initiative. Publisher Copyright: Copyright © 2021 Sánchez-Maldonado, Cáliz, López-Nevot, Cabrera-Serrano, Moñiz-Díez, Canhão, Ter Horst, Quartuccio, Sorensen, Glintborg, Hetland, Filipescu, Pérez-Pampin, Conesa-Zamora, Swierkot, den Broeder, De Vita, Petersen, Li, Ferrer, Escudero, Netea, Coenen, Andersen, Fonseca, Jurado, Bogunia-Kubik, Collantes and Sainz. |
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Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid ArthritisA Meta-Analysis of Two Large Cohortsdrug responsegenetic variantGWASrheumatoid arthritisTNF inhibitorsImmunology and AllergyImmunologyFunding Information: We thank all participants who have agreed to participate in this study. Authors also thank Mar?a Dolores Casares, ?ngeles Molina, Carmen Oloriz for the collection of Spanish samples and Hans Jurgen Hoffmann, Marianne Thomsen, Vibeke ?stergaard Thomsen, Malene Rohr Andersen, Lise Lotte B. Laursen, Helle J?rgensen, Ram Benny Christian Dessau, Niels Steen Krogh, Ulla Vogel, Paal Skytt Andersen, Ivan Brandslund, Steffen Bank, Frederik Trier M?ller, Nikolai Toft and Niels M?ller Andersen for the participation in collection and purification of Danish samples. We also thank the Danish Departments of Rheumatology for their implication in the collection of clinical data from RA patients included in the DANBIO cohort and the Danish Rheumatologic Biobank. Likewise, we would like to thank Teun van Herwaarden for steroid hormone measurements in serum samples from subjects ascertained through the HFGP initiative. Publisher Copyright: Copyright © 2021 Sánchez-Maldonado, Cáliz, López-Nevot, Cabrera-Serrano, Moñiz-Díez, Canhão, Ter Horst, Quartuccio, Sorensen, Glintborg, Hetland, Filipescu, Pérez-Pampin, Conesa-Zamora, Swierkot, den Broeder, De Vita, Petersen, Li, Ferrer, Escudero, Netea, Coenen, Andersen, Fonseca, Jurado, Bogunia-Kubik, Collantes and Sainz.We aimed to validate the association of 28 GWAS-identified genetic variants for response to TNF inhibitors (TNFi) in a discovery cohort of 1361 rheumatoid arthritis (RA) patients monitored in routine care and ascertained through the REPAIR consortium and DANBIO registry. We genotyped selected markers and evaluated their association with response to TNFi after 6 months of treatment according to the change in disease activity score 28 (ΔDAS28). Next, we confirmed the most interesting results through meta-analysis of our data with those from the DREAM cohort that included 706 RA patients treated with TNFi. The meta-analysis of the discovery cohort and DREAM registry including 2067 RA patients revealed an overall association of the LINC02549rs7767069 SNP with a lower improvement in DAS28 that remained significant after correction for multiple testing (per-allele ORMeta=0.83, PMeta=0.000077; PHet=0.61). In addition, we found that each copy of the LRRC55rs717117G allele was significantly associated with lower improvement in DAS28 in rheumatoid factor (RF)-positive patients (per-allele ORMeta=0.67, P=0.00058; PHet=0.06) whereas an opposite but not significant effect was detected in RF-negative subjects (per-allele ORMeta=1.38, P=0.10; PHet=0.45; PInteraction=0.00028). Interestingly, although the identified associations did not survive multiple testing correction, the meta-analysis also showed overall and RF-specific associations for the MAFBrs6071980 and CNTN5rs1813443 SNPs with decreased changes in DAS28 (per-allele ORMeta_rs6071980 = 0.85, P=0.0059; PHet=0.63 and ORMeta_rs1813443_RF+=0.81, P=0.0059; PHet=0.69 and ORMeta_rs1813443_RF-=1.00, P=0.99; PHet=0.12; PInteraction=0.032). Mechanistically, we found that subjects carrying the LINC02549rs7767069T allele had significantly increased numbers of CD45RO+CD45RA+ T cells (P=0.000025) whereas carriers of the LINC02549rs7767069T/T genotype showed significantly increased levels of soluble scavengers CD5 and CD6 in serum (P=0.00037 and P=0.00041). In addition, carriers of the LRRC55rs717117G allele showed decreased production of IL6 after stimulation of PBMCs with B burgdorferi and E coli bacteria (P=0.00046 and P=0.00044), which suggested a reduced IL6-mediated anti-inflammatory effect of this marker to worsen the response to TNFi. In conclusion, this study confirmed the influence of the LINC02549 and LRRC55 loci to determine the response to TNFi in RA patients and suggested a weak effect of the MAFB and CNTN5 loci that need to be further investigated.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Comprehensive Health Research Centre (CHRC) - pólo NMSCentro de Estudos de Doenças Crónicas (CEDOC)RUNSánchez-Maldonado, Jose ManuelCáliz, RafaelLópez-Nevot, Miguel ÁngelCabrera-Serrano, Antonio JoséMoñiz-Díez, AnaCanhão, HelenaTer Horst, RobQuartuccio, LucaSorensen, Signe B.Glintborg, BenteHetland, Merete LFilipescu, IleanaPérez-Pampin, EvaConesa-Zamora, PabloSwierkot, Jerzyden Broeder, Alfons A.De Vita, SalvatorePetersen, Eva Rabing BrixLi, YangFerrer, Miguel A.Escudero, AlejandroNetea, Mihai GCoenen, Marieke J.H.Andersen, VibekeFonseca, João E.Jurado, ManuelBogunia-Kubik, KatarzynaCollantes, EduardoSainz, Juan2021-12-22T23:25:40Z2021-10-272021-10-27T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/129663eng1664-3224PURE: 34925120https://doi.org/10.3389/fimmu.2021.672255info: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:RCAAP2024-03-11T05:08:44Zoai:run.unl.pt:10362/129663Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:46:36.228730Repositório 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 |
Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis A Meta-Analysis of Two Large Cohorts |
| title |
Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis |
| spellingShingle |
Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis Sánchez-Maldonado, Jose Manuel drug response genetic variant GWAS rheumatoid arthritis TNF inhibitors Immunology and Allergy Immunology |
| title_short |
Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis |
| title_full |
Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis |
| title_fullStr |
Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis |
| title_full_unstemmed |
Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis |
| title_sort |
Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis |
| author |
Sánchez-Maldonado, Jose Manuel |
| author_facet |
Sánchez-Maldonado, Jose Manuel Cáliz, Rafael López-Nevot, Miguel Ángel Cabrera-Serrano, Antonio José Moñiz-Díez, Ana Canhão, Helena Ter Horst, Rob Quartuccio, Luca Sorensen, Signe B. Glintborg, Bente Hetland, Merete L Filipescu, Ileana Pérez-Pampin, Eva Conesa-Zamora, Pablo Swierkot, Jerzy den Broeder, Alfons A. De Vita, Salvatore Petersen, Eva Rabing Brix Li, Yang Ferrer, Miguel A. Escudero, Alejandro Netea, Mihai G Coenen, Marieke J.H. Andersen, Vibeke Fonseca, João E. Jurado, Manuel Bogunia-Kubik, Katarzyna Collantes, Eduardo Sainz, Juan |
| author_role |
author |
| author2 |
Cáliz, Rafael López-Nevot, Miguel Ángel Cabrera-Serrano, Antonio José Moñiz-Díez, Ana Canhão, Helena Ter Horst, Rob Quartuccio, Luca Sorensen, Signe B. Glintborg, Bente Hetland, Merete L Filipescu, Ileana Pérez-Pampin, Eva Conesa-Zamora, Pablo Swierkot, Jerzy den Broeder, Alfons A. De Vita, Salvatore Petersen, Eva Rabing Brix Li, Yang Ferrer, Miguel A. Escudero, Alejandro Netea, Mihai G Coenen, Marieke J.H. Andersen, Vibeke Fonseca, João E. Jurado, Manuel Bogunia-Kubik, Katarzyna Collantes, Eduardo Sainz, Juan |
| author2_role |
author author author author author author author author author author author author author author 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) Comprehensive Health Research Centre (CHRC) - pólo NMS Centro de Estudos de Doenças Crónicas (CEDOC) RUN |
| dc.contributor.author.fl_str_mv |
Sánchez-Maldonado, Jose Manuel Cáliz, Rafael López-Nevot, Miguel Ángel Cabrera-Serrano, Antonio José Moñiz-Díez, Ana Canhão, Helena Ter Horst, Rob Quartuccio, Luca Sorensen, Signe B. Glintborg, Bente Hetland, Merete L Filipescu, Ileana Pérez-Pampin, Eva Conesa-Zamora, Pablo Swierkot, Jerzy den Broeder, Alfons A. De Vita, Salvatore Petersen, Eva Rabing Brix Li, Yang Ferrer, Miguel A. Escudero, Alejandro Netea, Mihai G Coenen, Marieke J.H. Andersen, Vibeke Fonseca, João E. Jurado, Manuel Bogunia-Kubik, Katarzyna Collantes, Eduardo Sainz, Juan |
| dc.subject.por.fl_str_mv |
drug response genetic variant GWAS rheumatoid arthritis TNF inhibitors Immunology and Allergy Immunology |
| topic |
drug response genetic variant GWAS rheumatoid arthritis TNF inhibitors Immunology and Allergy Immunology |
| description |
Funding Information: We thank all participants who have agreed to participate in this study. Authors also thank Mar?a Dolores Casares, ?ngeles Molina, Carmen Oloriz for the collection of Spanish samples and Hans Jurgen Hoffmann, Marianne Thomsen, Vibeke ?stergaard Thomsen, Malene Rohr Andersen, Lise Lotte B. Laursen, Helle J?rgensen, Ram Benny Christian Dessau, Niels Steen Krogh, Ulla Vogel, Paal Skytt Andersen, Ivan Brandslund, Steffen Bank, Frederik Trier M?ller, Nikolai Toft and Niels M?ller Andersen for the participation in collection and purification of Danish samples. We also thank the Danish Departments of Rheumatology for their implication in the collection of clinical data from RA patients included in the DANBIO cohort and the Danish Rheumatologic Biobank. Likewise, we would like to thank Teun van Herwaarden for steroid hormone measurements in serum samples from subjects ascertained through the HFGP initiative. Publisher Copyright: Copyright © 2021 Sánchez-Maldonado, Cáliz, López-Nevot, Cabrera-Serrano, Moñiz-Díez, Canhão, Ter Horst, Quartuccio, Sorensen, Glintborg, Hetland, Filipescu, Pérez-Pampin, Conesa-Zamora, Swierkot, den Broeder, De Vita, Petersen, Li, Ferrer, Escudero, Netea, Coenen, Andersen, Fonseca, Jurado, Bogunia-Kubik, Collantes and Sainz. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-12-22T23:25:40Z 2021-10-27 2021-10-27T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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http://hdl.handle.net/10362/129663 |
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eng |
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eng |
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1664-3224 PURE: 34925120 https://doi.org/10.3389/fimmu.2021.672255 |
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