Non-HLA gene polymorphisms in juvenile idiopathic arthritis: associations with disease outcome

M. Alberdi-Saugstrup; C. Enevold; M. Zak; S. Nielsen; E. Nordal; L. Berntson; A. Fasth; M. Rygg; K. Müller; on behalf of the Nordic Study Group of Pediatric Rheumatology (NoSPeR); on behalf of the Nordic Study Group of Pediatric Rheumatology (NoSPeR)

doi:10.1080/03009742.2016.1238959

Non-HLA gene polymorphisms in juvenile idiopathic arthritis: associations with disease outcome

M. Alberdi-Saugstrup^*, C. Enevold, M. Zak, S. Nielsen, E. Nordal, L. Berntson, A. Fasth, M. Rygg, K. Müller, on behalf of the Nordic Study Group of Pediatric Rheumatology (NoSPeR), on behalf of the Nordic Study Group of Pediatric Rheumatology (NoSPeR)

^*Corresponding author for this work

Department of Clinical Medicine

7 Citations (Scopus)

Abstract

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 language	English
Book series	Scandinavian Journal of Rheumatology
Volume	46
Issue number	5
Pages (from-to)	369-376
Number of pages	8
ISSN	0300-9742
DOIs	https://doi.org/10.1080/03009742.2016.1238959
Publication status	Published - 2017

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10.1080/03009742.2016.1238959

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Alberdi-Saugstrup, M., Enevold, C., Zak, M., Nielsen, S., Nordal, E., Berntson, L., Fasth, A., Rygg, M., Müller, K., on behalf of the Nordic Study Group of Pediatric Rheumatology (NoSPeR), & on behalf of the Nordic Study Group of Pediatric Rheumatology (NoSPeR) (2017). Non-HLA gene polymorphisms in juvenile idiopathic arthritis: associations with disease outcome. Scandinavian Journal of Rheumatology, 46(5), 369-376. https://doi.org/10.1080/03009742.2016.1238959

Alberdi-Saugstrup, M, Enevold, C, Zak, M, Nielsen, S, Nordal, E, Berntson, L, Fasth, A, Rygg, M, Müller, K, on behalf of the Nordic Study Group of Pediatric Rheumatology (NoSPeR) & on behalf of the Nordic Study Group of Pediatric Rheumatology (NoSPeR) 2017, 'Non-HLA gene polymorphisms in juvenile idiopathic arthritis: associations with disease outcome', Scandinavian Journal of Rheumatology, vol. 46, no. 5, pp. 369-376. https://doi.org/10.1080/03009742.2016.1238959

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title = "Non-HLA gene polymorphisms in juvenile idiopathic arthritis: associations with disease outcome",

abstract = "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.",

author = "M. Alberdi-Saugstrup and C. Enevold and M. Zak and S. Nielsen and E. Nordal and L. Berntson and A. Fasth and M. Rygg and K. M{\"u}ller and {on behalf of the Nordic Study Group of Pediatric Rheumatology (NoSPeR)} and {on behalf of the Nordic Study Group of Pediatric Rheumatology (NoSPeR)}",

year = "2017",

doi = "10.1080/03009742.2016.1238959",

language = "English",

volume = "46",

pages = "369--376",

journal = "Acta rheumatologica Scandinavica",

issn = "0301-3847",

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

PY - 2017

Y1 - 2017

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.

U2 - 10.1080/03009742.2016.1238959

DO - 10.1080/03009742.2016.1238959

M3 - Journal article

C2 - 28145159

AN - SCOPUS:85011255375

SN - 0301-3847

VL - 46

SP - 369

EP - 376

JO - Acta rheumatologica Scandinavica

JF - Acta rheumatologica Scandinavica

IS - 5

ER -

Non-HLA gene polymorphisms in juvenile idiopathic arthritis: associations with disease outcome

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