Genetic determinants for methotrexate response in juvenile idiopathic arthritis

Serena Pastore, Gabriele Stocco, Diego Favretto, Sara De Iudicibus, Andrea Taddio, Pio D'Adamo, Noelia Malusà, Riccardo Addobbati, Giuliana Decorti, Loredana Lepore, Alessandro Ventura

Research output: Contribution to journalArticle

Abstract

Juvenile idiopathic arthritis (JIAs) is the most common chronic rheumatic disease of childhood and is an important cause of disability. The folic acid analog methotrexate is the first choice disease-modifying anti-rheumatic drug in this disease, however, 35-45% of patients fail to respond. Molecular elements, such as variants in genes of pharmacological relevance, influencing response to methotrexate in JIA, would be important to individualize treatment strategies. Several studies have evaluated the effects of candidate genetic variants in the complex pathway of genes involved in methotrexate pharmacodynamics and pharmacokinetics, however, results are still contrasting and no definitive genetic marker of methotrexate response useful for the clinician to tailor therapy of children with JIA has been identified. Recently, genome-wide approaches have been applied, identifying new potential biological processes involved in methotrexate response in JIA such as TGF-beta signaling and calcium channels. If these genomic results are properly validated and integrated with innovative analyses comprising deep sequencing, epigenetics, and pharmacokinetics, they will greatly contribute to personalize therapy with methotrexate in children with JIA.

Original languageEnglish
Article number52
JournalFrontiers in Pharmacology
Volume6
Issue numberMAR
DOIs
Publication statusPublished - 2015

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Keywords

  • Gene expression profiling
  • Genome-wide association study
  • Juvenile idiopathic arthritis
  • Methotrexate
  • Pharmacogenomics

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Pastore, S., Stocco, G., Favretto, D., De Iudicibus, S., Taddio, A., D'Adamo, P., Malusà, N., Addobbati, R., Decorti, G., Lepore, L., & Ventura, A. (2015). Genetic determinants for methotrexate response in juvenile idiopathic arthritis. Frontiers in Pharmacology, 6(MAR), [52]. https://doi.org/10.3389/fphar.2015.00052