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Non-HLA gene polymorphisms in juvenile idiopathic arthritis: associations with disease outcome
Copenhagen University Hospital, Rigshospitalet, Department of Paediatrics and Adolescent Medicine; Naestved Hospital, Department of Paediatrics; Copenhagen University Hospital, Rigshospitalet, Institute for Inflammation Research.
Copenhagen University Hospital, Rigshospitalet, Institute for Inflammation Research.
Copenhagen University Hospital, Rigshospitalet, Department of Paediatrics and Adolescent Medicine.
Copenhagen University Hospital, Rigshospitalet, Department of Paediatrics and Adolescent Medicine.
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2017 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 46, no 5, p. 369-376Article in journal (Refereed) Published
Abstract [en]

Objective: To test the hypothesis that non-HLA single-nucleotide polymorphisms (SNPs) associated with the risk of juvenile idiopathic arthritis (JIA) are risk factors for an unfavourable disease outcome at long-term follow-up.

Methods: The Nordic JIA cohort is a prospective multicentre study cohort of patients from the Nordic countries. In all, 193 patients met the inclusion criteria of having an 8year follow-up assessment and available DNA sample. Seventeen SNPs met the inclusion criteria of having significant associations with JIA in at least two previous independent study cohorts. Clinical endpoints were disease remission, actively inflamed joints and joints with limitation of motion (LOM), articular or extra-articular damage, and history of uveitis.

Results: Evidence of associations between genotypes and endpoints were found for STAT4, ADAD1-IL2-IL21, PTPN2, and VTCN1 (p=0.003-0.05). STAT4_rs7574865 TT was associated with the presence of actively inflamed joints [odds ratio (OR) 20.6, 95% confidence interval (CI) 2.2->100, p=0.003] and extra-articular damage (OR 7.9, 95% CI 1-56.6, p=0.057). ADAD1_rs17388568 AA was associated with a lower risk of having joints with LOM (OR 0.1, 95% CI 0-0.55, p=0.016). PTPN2_rs1893217 CC was associated with a lower risk of having joints with LOM (OR 0.2, 95% CI 0-0.99, p=0.026), while VTCN1_rs2358820 GA was associated with uveitis (OR 3.5, 95% CI 1-12.1, p=0.029).

Conclusion: This exploratory study, using a prospectively followed JIA cohort, found significant associations between long-term outcome and SNPs, all previously associated with development of JIA and involved in immune regulation and signal transduction in immune cells.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD , 2017. Vol. 46, no 5, p. 369-376
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:uu:diva-335764DOI: 10.1080/03009742.2016.1238959ISI: 000411129500006PubMedID: 28145159OAI: oai:DiVA.org:uu-335764DiVA, id: diva2:1166486
Note

Published on behalf of the Nordic Study Group of Pediatric Rheumatology (NoSPeR)

Available from: 2017-12-15 Created: 2017-12-15 Last updated: 2017-12-15Bibliographically approved

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