Sistema de Salut de Catalunya
Institut Català de la Salut
[Salvador-Martín S, Kaczmarczyk B] Pharmacy Department, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain. [Álvarez R] Genomics Unit, Spanish Nacional Center for Cardiovascular Diseases (CNIC), 28029 Madrid, Spain. [Navas-López VM] Pediatric Gastroenterology and Nutrition Unit, Hospital Regional Universitario de Málaga, IBIMA Multidisciplinary Group for Pediatric Research, 29010 Málaga, Spain. [Gallego-Fernández C] Pharmacy Department, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain. [Moreno-Álvarez A] Pediatric Gastroenterology Unit, Department of Pediatrics, A Coruña University Hospital, 15006 A Coruña, Spain. [Clemente S] Servei de Farmàcia, Vall d’Hebron Hospital Universitari, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2021-05-17T12:17:43Z
2021-05-17T12:17:43Z
2021-01-08
Biomarcador; Expressió gènica; Malaltia inflamatòria intestinal
Biomarcador; Expresión génica; Enfermedad inflamatoria intestinal
Biomarker; Gene expression; Inflammatory bowel disease
Background: Up to 30% of patients with pediatric inflammatory bowel disease (IBD) do not respond to anti-Tumor Necrosis Factor (anti-TNF) therapy. The aim of this study was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD. Methods: An observational, longitudinal, prospective cohort study was conducted. The study population comprised 38 patients with IBD aged < 18 years who started treatment with infliximab or adalimumab (29 responders and nine non-responders). Whole gene expression profiles from total RNA isolated from whole blood samples of six responders and six non-responders taken before administration of the biologic and after two weeks of therapy were analyzed using next-generation RNA sequencing. The expression of six selected genes was measured for purposes of validation in all of the 38 patients recruited using qPCR. Results: Genes were differentially expressed in non-responders and responders (32 before initiation of treatment and 44 after two weeks, Log2FC (Fold change) >0.6 or <−0.6 and p value < 0.05). After validation, FCGR1A, FCGR1B, and GBP1 were overexpressed in non-responders two weeks after initiation of anti-TNF treatment (Log2FC 1.05, 1.21, and 1.08, respectively, p value < 0.05). Conclusion: Expression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.
This research was funded by Instituto de Salud Carlos III (grants numbers PI16/00559 and PI19/00792), Consejería de Educación y Deporte de la Comunidad de Madrid (grant number PEJ16/MED/AI-1260), and by the Gregorio Marañón Health Research Institute (grant number PRE-2018-2). The study was cofunded by European Regional Develompment Funds (FEDER) from the European Commission, “A way of making Europe”.
Article
Published version
English
Intestins - Inflamació; Medicaments - Administració; Adolescents; DISEASES::Digestive System Diseases::Gastrointestinal Diseases::Gastroenteritis::Inflammatory Bowel Diseases; Other subheadings::Other subheadings::Other subheadings::/drug therapy; NAMED GROUPS::Persons::Age Groups::Adolescent; ENFERMEDADES::enfermedades del sistema digestivo::enfermedades gastrointestinales::gastroenteritis::enfermedad inflamatoria intestinal; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; DENOMINACIONES DE GRUPOS::personas::Grupos de Edad::adolescente
MDPI
Pharmaceutics;13(1)
https://doi.org/10.3390/pharmaceutics13010077
info:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F00559
info:eu-repo/grantAgreement/ES/PE2017-2020/PI19%2F00792
info:eu-repo/grantAgreement/ES/PE2013-2016/PEJ16%2FMED%2FAI-1260
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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