title: Genetic determinants for methotrexate response in juvenile idiopathic arthritis.
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.
authors: Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste Italy.
authors: Serena
authors: S
authors: Pastore
authors: Department of Life Sciences, University of Trieste, Trieste Italy.
authors: Gabriele
authors: G
authors: Stocco
authors: Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste Italy.
authors: Diego
authors: D
authors: Favretto
authors: Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste Italy.
authors: Sara
authors: S
authors: De Iudicibus
authors: Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste Italy ; Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste Italy.
authors: Andrea
authors: A
authors: Taddio
authors: Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste Italy ; Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste Italy.
authors: Pio
authors: P
authors: d'Adamo
authors: Department of Prevention, Azienda Servizi Sanitari 1, Trieste Italy.
authors: Noelia
authors: N
authors: Malusà
authors: Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste Italy.
authors: Riccardo
authors: R
authors: Addobbati
authors: Department of Life Sciences, University of Trieste, Trieste Italy.
authors: Giuliana
authors: G
authors: Decorti
authors: Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste Italy.
authors: Loredana
authors: L
authors: Lepore
authors: Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste Italy ; Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste Italy.
authors: Alessandro
authors: A
authors: Ventura
keywords: gene expression profiling; genome-wide association study; juvenile idiopathic arthritis; methotrexate; pharmacogenomics