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5-Aminoimidazole-4-carboxamide ribonucleotide-transformylase and inosine-triphosphate-pyrophosphatase genes variants predict remission rate during methotrexate therapy in patients with juvenile idiopathic arthritis

  • Original Article - Genes and Disease
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A Letter to the Editor - Genes and Disease to this article was published on 09 July 2015

Abstract

For children with juvenile idiopathic arthritis (JIA) who fail to respond to methotrexate, the delay in identifying the optimal treatment at an early stage of disease can lead to long-term joint damage. Recent studies indicate that relevant variants to predict methotrexate response in JIA are those in 5-aminoimidazole-4-carboxamide ribonucleotide-transformylase (ATIC), inosine-triphosphate-pyrophosphatase (ITPA) and solute-liquid-carrier-19A1 genes. The purpose of the study was, therefore, to explore the role of these candidate genetic factors on methotrexate response in an Italian cohort of children with JIA. Clinical response to methotrexate was evaluated as clinical remission stable for a 6-month period, as ACRPed score and as change in Juvenile Arthritis Disease score. The most relevant SNPs for each gene considered were assayed on patients’ DNA. ITPA activity was measured in patients’ erythrocytes. Sixty-nine patients with JIA were analyzed: 52.2 % responded to therapy (ACRPed70 score), while 37.7 % reached clinical remission stable for 6 months. ATIC rs2372536 GG genotype was associated with improved clinical remission (adjusted p value = 0.0090). For ITPA, rs1127354 A variant was associated with reduced clinical remission: (adjusted p value = 0.028); this association was present even for patients with wild-type ITPA and low ITPA activity. These preliminary results indicate that genotyping of ATIC rs2372536 and ITPA rs1127354 variants or measuring ITPA activity could be useful to predict methotrexate response in children with JIA after validation by further prospective studies on a larger patient cohort.

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Acknowledgments

This study was supported by grants from the Italian Ministry of Health and by a donation from foundation Alberto and Kathleen Casali, Trieste, Italy.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. University of Trieste, Trieste, Italy

    Serena Pastore, Valentina Moressa & Alessandro Ventura

  2. Institute for Maternal and Child Health, IRCCS “Burlo Garofolo”, Trieste, Italy

    Serena Pastore, Diego Favretto, Loredana Lepore & Alessandro Ventura

  3. Department of Life Sciences, University of Trieste, Via A. Fleming 22, 34127, Trieste, Italy

    Gabriele Stocco, Luigi Zandonà & Giuliana Decorti

  4. Department of Prevention, Sanitary Services Agency 1, Via della Pietà 2/2, 34129, Trieste, Italy

    Noelia Malusà

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  1. Serena Pastore
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Correspondence to Gabriele Stocco.

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Pastore, S., Stocco, G., Moressa, V. et al. 5-Aminoimidazole-4-carboxamide ribonucleotide-transformylase and inosine-triphosphate-pyrophosphatase genes variants predict remission rate during methotrexate therapy in patients with juvenile idiopathic arthritis. Rheumatol Int 35, 619–627 (2015). https://doi.org/10.1007/s00296-014-3131-y

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  • DOI: https://doi.org/10.1007/s00296-014-3131-y

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