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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Non-HLA gene polymorphisms in juvenile idiopathic arthritis: associations with disease outcome

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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 8 year 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.

Original languageEnglish
JournalScandinavian Journal of Rheumatology
Volume46
Issue number5
Pages (from-to)369-376
Number of pages8
ISSN0300-9742
DOIs
Publication statusPublished - Sep 2017

    Research areas

  • Adolescent, Arthritis, Juvenile, Child, Female, Genetic Predisposition to Disease, Humans, Immunity, Male, Patient Acuity, Polymorphism, Single Nucleotide, Prospective Studies, Protein Tyrosine Phosphatase, Non-Receptor Type 2, STAT4 Transcription Factor, Scandinavian and Nordic Countries, V-Set Domain-Containing T-Cell Activation Inhibitor 1, Journal Article, Multicenter Study

ID: 52174958