Increased frequency of extremely skewed X chromosome inactivation in juvenile idiopathic arthritis

Arthritis Rheum. 2009 Nov;60(11):3410-2. doi: 10.1002/art.24956.

Abstract

Objective: Juvenile idiopathic arthritis (JIA) is a childhood rheumatic disease of unknown etiology. Two subgroups of JIA, i.e., oligoarticular and polyarticular, are thought to have an autoimmune component, and show a higher female:male ratio. Skewed X chromosome inactivation (XCI) has previously been shown to be associated with scleroderma and autoimmune thyroiditis, 2 autoimmune disorders occurring predominantly in females. This study was undertaken to extend the analysis to the pediatric age group and to determine the XCI profiles of patients with JIA.

Methods: A polymorphic repeat in the androgen receptor gene was genotyped to determine XCI status in 81 female patients with JIA (21 with polyarticular disease and 60 with oligoarticular disease) and 211 healthy female controls. DNA obtained from venous blood samples was used for this analysis.

Results: Informative data were obtained on 62 JIA patients and 155 controls. Skewed XCI was observed in 14 patients (22.6%) and 11 controls (7.1%) (P = 0.0036), and extreme skewing was apparent in 8 patients (12.9%) and 2 controls (1.3%) (P = 0.0008).

Conclusion: Our findings in the present study indicate that skewed XCI may be a risk factor for the occurrence of autoimmune disorders, including JIA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Arthritis, Juvenile / epidemiology
  • Arthritis, Juvenile / genetics*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Chromosomes, Human, X / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Heterozygote
  • Humans
  • Mutation / genetics
  • Receptors, Androgen / genetics
  • Risk Factors
  • X Chromosome Inactivation / genetics*

Substances

  • Receptors, Androgen