title: Genetic variation in VTCN1 (B7-H4) is associated with course of disease in juvenile idiopathic arthritis.
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.
authors.affiliation: Department of Paediatrics/Paediatric Rheumatology, Leiden University Medical Center, , Leiden, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: Albers
authors.forename: T H C M
authors.initials: TH
authors.lastname: Reinards
authors.forename: D M C
authors.initials: DM
authors.lastname: Brinkman
authors.forename: S S M
authors.initials: SS
authors.lastname: Kamphuis
authors.forename: M A J
authors.initials: MA
authors.lastname: van Rossum
authors.forename: E P A H
authors.initials: EP
authors.lastname: Hoppenreijs
authors.forename: H J
authors.initials: HJ
authors.lastname: Girschick
authors.forename: C
authors.initials: C
authors.lastname: Wouters
authors.forename: R K
authors.initials: RK
authors.lastname: Saurenmann
authors.forename: E
authors.initials: E
authors.lastname: Bakker
authors.forename: W
authors.initials: W
authors.lastname: Verduijn
authors.forename: P
authors.initials: P
authors.lastname: Slagboom
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: R E M
authors.initials: RE
authors.lastname: Toes
authors.forename: J J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
authors.forename: R
authors.initials: R
authors.lastname: ten Cate
authors.forename: M W
authors.initials: MW
authors.lastname: Schilham
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000235:genetics*
chemical_list: D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6
keywords: Arthritis; Disease Activity; Gene Polymorphism; Juvenile Idiopathic Arthritis; T Cells