Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept

Autor: F. Navarro-Sarabia, Javier Martín, Patricia Carreira, Juan J. Gomez-Reino, Juan D. Cañete, Juan José Alegre-Sancho, Lara Valor, Dora Pascual-Salcedo, Francisco J. Blanco, Antonio Gonzalez, Beatriz Joven, Yiannis Vasilopoulos, Javier Narváez, Alejandro Balsa, Miguel Ferrer, Ariana Montes, Sara Manrique-Arija, César Magro-Checa, María del Carmen Ordóñez, Ana Márquez, Moreira Vf, Rafael Cáliz, Aida Ferreiro-Iglesias, Rosa Garcia-Portales, Manuel J. Moreno-Ramos, Eva Perez-Pampin, Enrique Raya
Přispěvatelé: Instituto de Salud Carlos III, European Commission, Carreira, P. [0000-0001-8279-3806], Blanco, Francisco J. [0000-0001-9821-7635], Márquez, Ana [0000-0001-9913-7688], Martín, J. [0000-0002-2202-0622], González, Antonio [0000-0002-2624-0606], Universitat de Barcelona, Carreira, P., Blanco, Francisco J., Márquez, Ana, Martín, J., González, Antonio, UAM. Departamento de Medicina
Rok vydání: 2019
Předmět:
0301 basic medicine
Oncology
Male
Heredity
Pharmacogenomic Variants
Antibody Response
Genome-wide association study
Biochemistry
Etanercept
Arthritis
Rheumatoid
0302 clinical medicine
arthritis
Reumatoid
Mathematical and Statistical Techniques
Medicine and Health Sciences
Single nucleotide
Immune Response
Aged
80 and over
Multidisciplinary
Statistics
Biochemical markers
tumor Necrosis Factor-alpha
Genomics
Metaanalysis
Middle Aged
Rheumatoid arthritis
Arthritis rheumatoid
Antirheumatic Agents
Physical Sciences
Marcadors bioquímics
Medicine
Female
medicine.drug
Research Article
Adult
Genetic Markers
medicine.medical_specialty
Medicina
Science
Immunology
Single-nucleotide polymorphism
Rheumatoid Arthritis
Artritis reumatoide
Research and Analysis Methods
Polymorphism
Single Nucleotide
Autoimmune Diseases
Molecular Genetics
03 medical and health sciences
Young Adult
Rheumatology
Internal medicine
medicine
Adalimumab
Genome-Wide Association Studies
Genetics
SNP
Humans
Polymorphism
Statistical Methods
Genomes
Molecular Biology
Aged
030203 arthritis & rheumatology
business.industry
Tumor Necrosis Factor-alpha
Arthritis
arthritis RA
Biology and Life Sciences
Computational Biology
Human Genetics
medicine.disease
Genome Analysis
Infliximab
Pharmacogenomic Testing
030104 developmental biology
Genetic Loci
Clinical Immunology
Clinical Medicine
business
Pharmacogenetics
Mathematics
Biomarkers
Genome-Wide Association Study
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
Dipòsit Digital de la UB
Universidad de Barcelona
Recercat. Dipósit de la Recerca de Catalunya
PLoS One
r-FISABIO: Repositorio Institucional de Producción Científica
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
PLoS ONE
Biblos-e Archivo. Repositorio Institucional de la UAM
r-FISABIO. Repositorio Institucional de Producción Científica
PLoS ONE, Vol 14, Iss 2, p e0213073 (2019)
RUC. Repositorio da Universidade da Coruña
ISSN: 1932-6203
Popis: Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNPs.
This work was supported by the Instituto de Salud Carlos III (ISCIII, Spain) through grants PI14/01651, PI17/01606 and RD16/0012/0014 to AG and PI12/01909 to JJG-R. These grants are partially financed by the European Regional Development Fund of the EU (FEDER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Databáze: OpenAIRE
Externí odkaz: