TY - JOUR

T1 - Non-HLA gene polymorphisms in juvenile idiopathic arthritis

T2 - associations with disease outcome

AU - Alberdi-Saugstrup, M

AU - Enevold, C

AU - Zak, M

AU - Nielsen, S

AU - Nordal, E

AU - Berntson, L

AU - Fasth, A

AU - Rygg, M

AU - Müller, K

AU - Nordic Study Group of Pediatric Rheumatology (NoSPeR)

PY - 2017/9

Y1 - 2017/9

N2 - 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.

AB - 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.

KW - Adolescent

KW - Arthritis, Juvenile

KW - Child

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Immunity

KW - Male

KW - Patient Acuity

KW - Polymorphism, Single Nucleotide

KW - Prospective Studies

KW - Protein Tyrosine Phosphatase, Non-Receptor Type 2

KW - STAT4 Transcription Factor

KW - Scandinavian and Nordic Countries

KW - V-Set Domain-Containing T-Cell Activation Inhibitor 1

KW - Journal Article

KW - Multicenter Study

U2 - 10.1080/03009742.2016.1238959

DO - 10.1080/03009742.2016.1238959

M3 - Journal article

VL - 46

SP - 369

EP - 376

JO - Scandinavian Journal of Rheumatology

JF - Scandinavian Journal of Rheumatology

SN - 0300-9742

IS - 5

ER -