Association of RANTES promoter polymorphism with juvenile rheumatoid arthritis

Arthritis Rheum. 2009 Apr;60(4):1173-8. doi: 10.1002/art.24422.

Abstract

Objective: We recently reported that RANTES was a key molecule in the pathogenesis of juvenile rheumatoid arthritis (JRA) in a longitudinal cohort. This study was undertaken to investigate genetic associations between the RANTES -28 C/G and -403 G/A polymorphisms and JRA in a well-documented cohort of patients who were followed up prospectively.

Methods: Patients with JRA (n = 107) and healthy children (n = 139) were genotyped through use of a polymerase chain reaction-based assay. Association of the RANTES promoter polymorphisms with results of laboratory tests, clinical variables, outcome after clinical remission, and response to intraarticular triamcinolone injection was evaluated in patients who were followed up for >1 year.

Results: JRA patients had a significantly higher frequency of the RANTES -28 G/G genotype, as compared with ethnically matched healthy controls. The RANTES -28 C/G polymorphism was associated with the duration of clinical remission, with patients carrying the RANTES -28G allele experiencing only 49% of the duration of remission experienced by patients who were RANTES -28 C/C homozygous. The RANTES -28 C/G polymorphism was associated with the duration of clinical response to intraarticular triamcinolone injection, with patients carrying the RANTES -28G allele showing shorter duration of clinical response. No significant association between the RANTES -403 G/A polymorphism and JRA was found in this Chinese population.

Conclusion: Our findings indicate that the RANTES -28 C/G polymorphism represents a genetic risk factor for JRA. It is noteworthy that this RANTES promoter polymorphism was also associated with an early relapse of disease after clinical remission and a shorter duration of clinical response to intraarticular administration of corticosteroids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Arthritis, Juvenile / drug therapy
  • Arthritis, Juvenile / ethnology*
  • Arthritis, Juvenile / genetics*
  • Asian People / genetics*
  • Chemokine CCL5 / genetics*
  • Child
  • Female
  • Genetic Predisposition to Disease / ethnology
  • Genotype
  • Homozygote
  • Humans
  • Male
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics
  • Prospective Studies
  • Recurrence
  • Remission Induction
  • Risk Factors
  • Taiwan / epidemiology

Substances

  • Adrenal Cortex Hormones
  • CCL5 protein, human
  • Chemokine CCL5