دورية أكاديمية
Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis: A Meta-Analysis of Two Large Cohorts
| العنوان: | Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis: A Meta-Analysis of Two Large Cohorts |
|---|---|
| المؤلفون: | 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 |
| المساهمون: | Sánchez-Maldonado,JM, Cáliz,R, Cabrera-Serrano,AJ, Moñiz-Díez,A, Jurado,M, Sainz,J Genomic Oncology Area, Centre for Genomics and Oncological Research (GENYO), Parque tecnológico de la Salud (PTS) Granada, Granada, Spain. Sánchez-Maldonado,JM, Sainz,J Hematology Department, Virgen de las Nieves University Hospital, Granada, Spain. Sánchez-Maldonado,JM, López-Nevot,MA, Sainz,J Instituto de Investigación Biosanitaria (IBs) Granada, Granada, Spain. Cáliz,R Department of Rheumatology, Virgen de las Nieves University Hospital, Granada, Spain. López-Nevot,MA Immunology Department, Virgen de las Nieves University Hospital, Granada, Spain. Canhão,H EpiDoC Unit, CEDOC, NOVA Medical School and National School of Public Health, Universidade Nova de Lisboa, Lisbon, Portugal. Canhão,H Comprehensive Health Research Center (CHRC), NOVA Medical School, Lisbon, Portugal. Ter Horst,R, Li,Y, Netea,MG Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands. Quartuccio,L, De Vita,S, Andersen,V Department of Medical Area, Clinic of Rheumatology, University of Udine, Udine, Italy. Sorensen,SB, Andersen,V Molecular Diagnostic and Clinical Research Unit, IRS-Center Sonderjylland, University Hospital of Southern Jutland, Aabenraa, Denmark. Sorensen,SB Institute of Molecular Medicine, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. Glintborg,B, Hetland,ML The Danish Rheumatologic Biobank and Copenhagen Center for Arthritis Research (DANBIO) Registry, The Danish Rheumatologic Biobank and Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Rigshospitalet, Glostrup, Denmark. Glintborg,B, Hetland,ML Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Filipescu,I Rheumatology Department, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania. Pérez-Pampin,E Rheumatology Unit, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain. Conesa-Zamora,P Clinical Analysis Department, Santa Lucía University Hospital, Cartagena, Spain. Swierkot,J Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland. den Broeder,AA Radboud Institute for Health Sciences, Department of Rheumatology, Radboud University Medical Center, Nijmegen, Netherlands. Petersen,ERB Department of Biochemistry and Immunology, University Hospital of Southern Jutland, Aabenraa, Denmark. Li,Y Centre for Individualised Infection Medicine (CiiM) & Centre for Experimental and Clinical Infection Research (TWINCORE), Helmholtz-Centre for Infection Research (HZI) and The Hannover Medical School (MHH), Hannover, Germany. Escudero,A, Collantes,E Rheumatology Department, Reina Sofía Hospital/Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)/University of Córdoba, Córdoba, Spain. Netea,MG Department for Immunology & Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany. Coenen,MJH Radboud Institute for Health Sciences, Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands. Andersen,V Institute of Regional Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. Fonseca,JE Rheumatology and Metabolic Bone Diseases Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte (CHLN), Lisbon, Portugal. Fonseca,JE Rheumatology Research Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon Academic Medical Center, Lisbon, Portugal. Bogunia-Kubik,K Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland, Sainz,J Department of Biochemistry and Molecular Biology I, University of Granada, Granada, Spain., This study was supported by grants PI17/02276 and PI20/01845 from Fondo de Investigaciones Sanitarias (Madrid, Spain) and by intramural funds of GENYO and FIBAO foundation (Granada, Spain). This study was also supported by the Novo Nordisk Fonden (NNF15OC0016932, VA) and Knud og Edith Eriksens Mindefond (VA) and Gigtforeningen (A2037, A3570, VA). JS and KB-K were supported by the grant No. 2016/21/B/NZ5/01901 from the National Science Centre (Poland). MGN was supported by a Spinoza grant from the Netherlands Organization for Scientific Research. YL was supported by an ERC Starting Grant (948207) and the Radboud University Medical Centre Hypatia Grant (2018) for Scientific Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| بيانات النشر: | Frontiers |
| سنة النشر: | 2021 |
| المجموعة: | Sistema Sanitario Público de Andalucía (SSPA): Repositorio |
| مصطلحات موضوعية: | GWAS, Genetic variant, Rheumatoid arthritis, Drug response, TNF inhibitors, Rheumatoid factor, Escherichia coli, Polymorphism, single nucleotide, Alleles, Variantes farmacogenómicas, Artritis reumatoide, Biomarcadores farmacológicos, Inhibidores del factor de necrosis tumoral, Factor reumatoide, Polimorfismo de nucleótido simple, Alelos, Medical Subject Headings::Persons::Persons::Age Groups::Adult, Medical Subject Headings::Persons::Persons::Age Groups::Adult::Aged, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles, Medical Subject Headings::Diseases::Musculoskeletal Diseases::Rheumatic Diseases::Arthritis, Rheumatoid, Medical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, Pharmacological, Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies, Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility, Medical Subject Headings::Check Tags::Female, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation |
| الوصف: | 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document; application/vnd.openxmlformats-officedocument.spreadsheetml.sheet |
| اللغة: | English |
| تدمد: | 1664-3224 |
| العلاقة: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.672255/fullTest; Sánchez-Maldonado JM, Cáliz R, López-Nevot MÁ, Cabrera-Serrano AJ, Moñiz-Díez A, Canhão H, et al. Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis: A Meta-Analysis of Two Large Cohorts. Front Immunol. 2021 Oct 27;12:672255; http://hdl.handle.net/10668/4535Test; PMC8579100 |
| DOI: | 10.3389/fimmu.2021.672255 |
| الإتاحة: | https://doi.org/10.3389/fimmu.2021.672255Test http://hdl.handle.net/10668/4535Test |
| حقوق: | Atribución 4.0 Internacional ; http://creativecommons.org/licenses/by/4.0Test/ ; open access |
| رقم الانضمام: | edsbas.6914237 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 16643224 |
|---|---|
| DOI: | 10.3389/fimmu.2021.672255 |