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Genetic variation in VTCN1 (B7-H4) is associated with course of disease in juvenile idiopathic arthritis
  1. H M Albers1,
  2. T H C M Reinards1,
  3. D M C Brinkman2,
  4. S S M Kamphuis3,
  5. M A J van Rossum4,
  6. E PA H Hoppenreijs5,
  7. H J Girschick6,
  8. C Wouters7,
  9. R K Saurenmann8,
  10. E Bakker9,
  11. W Verduijn10,
  12. P Slagboom11,
  13. T W J Huizinga12,
  14. R E M Toes12,
  15. J J Houwing-Duistermaat13,
  16. R ten Cate1,
  17. M W Schilham14
  1. 1Department of Paediatrics/Paediatric Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Paediatrics/Paediatric Rheumatology, Rijnland Hospital, Leiderdorp, The Netherlands
  3. 3Department of Paediatrics/Paediatric Rheumatology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands
  4. 4Department of Paediatrics/Paediatric Rheumatology, Emma Children's Hospital/Academic Medical Centre and Reade (Jan van Breemen location), Amsterdam, The Netherlands
  5. 5Department of Paediatrics/Paediatric Rheumatology, St Maartenskliniek and Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  6. 6Vivantes Children's Hospital, Berlin-Friedrichshain, Germany
  7. 7University Hospital Gasthuisberg, Leuven, Belgium
  8. 8Zürich University Children's Hospital, Zürich, Switzerland
  9. 9Centre for Human and Clinical Genetics—Laboratory for Diagnostic Genome Analysis, Leiden University Medical Center, Leiden, The Netherlands
  10. 10Department of Immunohematology and Blood transfusion, Leiden University Medical Center, Leiden, The Netherlands
  11. 11Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
  12. 12Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  13. 13Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands
  14. 14Department of Paediatrics/Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Dr Marco W Schilham, Department of Pediatrics, P3-P, Leiden University Medical Center, PO Box 9600, 2300RC, Leiden, The Netherlands; M.W.Schilham{at}lumc.nl

Abstract

Objective The course of disease in juvenile idiopathic arthritis (JIA) is unpredictable with episodes of activity and remission. In order to identify predictive factors, 93 SNPs, JIA subtype, age at onset and ANA status were studied in relation to disease course.

Methods Genetic and clinical parameters were analysed in a cohort of 272 Caucasian patients with persistent oligoarthritis (n=129), extended oligoarthritis (n=57) and rheumatoid factor negative polyarthritis (n=86). Categories of disease course (remitting (n=65), intermediate (n=96) and unremitting (n=111)) were designed based on the cumulative time spent in active disease in the first 2 years.

Results Univariate analysis revealed association of the course of disease with JIA subtype (p=5.7*10–5) and three SNPs; VTCN1 rs10 923 223 (p=4.4*10−5), VTCN1 rs12 046 117 (p=0.017) and CDK6 rs42 041 (p=0.038). In a subsequent multivariate ordinal logistic regression analysis, VTCN1 rs10 923 223 (OR 0.41, 95%-CI 0.26 to 0.63) and JIA subtype (OR 3.8, 95%-CI 2.0 to 7.2; OR 2.5, 95%-CI 1.4 to 4.2, for extended oligoarthritis and RF-negative polyarthritis vs persistent oligoarthritis, respectively) were the strongest independent factors for course of disease.

Conclusions This study provides evidence that VTCN1, encoding B7-H4, is associated with course of disease in selected subtypes of JIA. VTCN1 might be useful in predicting the course of disease.

  • Juvenile Idiopathic Arthritis
  • T Cells
  • Gene Polymorphism
  • Arthritis
  • Disease Activity

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