title: IL1 and TNF gene polymorphisms in patients with juvenile idiopathic arthritis treated with TNF inhibitors.
abstract: OBJECTIVE
  To investigate the genetic contribution of cytokine gene polymorphisms (interleukin 1 (IL1) and tumour necrosis factor alpha (TNFalpha)) on disease phenotype and on response to TNF-blocking agents in a population of patients with juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  A cohort of 107 consecutive patients with JIA who were receiving treatment with anti-TNF agents was enrolled in this study. Analysis of genetic polymorphisms for IL1B +3954, IL1RA +2018, TNFalpha -238 and TNFalpha -308 was performed by enzyme-linked oligo sorbent assay, and compared with those obtained from 630 healthy Caucasians and 263 adult patients with rheumatoid arthritis. Relevant demographic, clinical and laboratory data were collected from clinical charts and entered into a customised database, and chi(2) analysis was performed to compare cytokine polymorphisms with disease type according to the International League of Associations for Rheumatology criteria, presence of uveitis, rheumatoid factor and anti-nuclear antibody positivity, erosive disease, frequency of adverse effects to anti-TNF and clinical response after 3 months.
  
  
  RESULTS
  The T/T genotype of the IL1B +3954 polymorphism was absent in patients with JIA and present in 5% of controls (p = 0.015). No significant correlation was found between the studied polymorphisms and clinical or laboratory variables considered. Clinical response to TNF inhibitors at 3 months was not associated with the genetic polymorphisms considered.
  
  
  CONCLUSIONS
  In our cohort, the absence of the rare IL1B +3954 gene polymorphism was associated with JIA, but without specificity to particular disease phenotypes. The TNF and IL1 gene polymorphism studied did not seem to be associated with response to anti-TNF treatment.
authors.affiliation: Unité Mixte Hospices Civils de Lyon-BioMérieux, Lyon, France. roland.cimaz@chu-lyon.fr
authors.forename: Rolando
authors.initials: R
authors.lastname: Cimaz
authors.forename: Marie-Angélique
authors.initials: MA
authors.lastname: Cazalis
authors.forename: Charlotte
authors.initials: C
authors.lastname: Reynaud
authors.forename: Valeria
authors.initials: V
authors.lastname: Gerloni
authors.forename: Francesco
authors.initials: F
authors.lastname: Zulian
authors.forename: Martina
authors.initials: M
authors.lastname: Biggioggero
authors.forename: Giorgia
authors.initials: G
authors.lastname: Martini
authors.forename: Irene
authors.initials: I
authors.lastname: Pontikaki
authors.forename: Flavio
authors.initials: F
authors.lastname: Fantini
authors.forename: Bruno
authors.initials: B
authors.lastname: Mougin
authors.forename: Pierre
authors.initials: P
authors.lastname: Miossec
mesh_terms: D000293:Adolescent; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D018501:Antirheumatic Agents; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha