title: TNF-α gene polymorphisms and juvenile idiopathic arthritis: Influence on disease outcome and therapeutic response.
abstract: OBJECTIVE
  To investigate the genetic contribution of TNF-α gene polymorphisms on the disease course and therapeutic response in patients with juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  74 Caucasian patients with JIA were recruited with a control group of 77 healthy children. DNA was extracted for analysis of TNF-α gene promoter polymorphisms at positions -163, -244, -238, -376, and -308.
  
  
  RESULTS
  No SNPs at position -163 were observed, while we observed only SNPs at positions -244 and -376 in the controls. No differences were observed in the prevalence of SNPs at -238 and -308 between JIA and controls. In JIA patients no significant differences were observed between the -238 and -308 G/A genotypes and different disease phenotypes. We observed a significant lower disease activity expressed in the carriers of -308 GG genotype with respect to GA and AA genotypes after 6 (p = 0.008 and p = 0.013, respectively) and 12 months of disease (p = 0.02 and p = 0.08, respectively). Also the -238 GG genotypes showed a better disease course after 12 months of disease. Moreover, the -238/-308 GG genotypes presented the higher reduction of disease activity both after 6 (p < 0.01 vs GA and p < 0.01 vs AA) and 12 months from baseline (p < 0.01 vs GA and p < 0.01 vs AA). After 12 months of biologic therapy, a significant higher disease activity was observed in patients with genotype -308 AA respect to both GA (p = 0.012) and GG (p = 0.016).
  
  
  CONCLUSIONS
  JIA patients carrying the TNF-α -308 GA/AA and -238 GA genotypes are associated with a worse prognosis and with a lower response to anti-TNF-α drugs.
authors.affiliation: Paediatric Rheumatology Unit, Department of Paediatrics, "G. d'Annunzio" University, Chieti-Pescara, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Scardapane
authors.affiliation: Laboratory of Molecular Genetics, Department of Psychological, Humanities and Territorial Sciences, "G. d'Annunzio" University, Chieti-Pescara, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Ferrante
authors.affiliation: Paediatric Rheumatology Unit, Department of Paediatrics, "G. d'Annunzio" University, Chieti-Pescara, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Nozzi
authors.affiliation: Paediatric Rheumatology Unit, Department of Paediatrics, "G. d'Annunzio" University, Chieti-Pescara, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Savino
authors.affiliation: Laboratory of Molecular Genetics, Department of Psychological, Humanities and Territorial Sciences, "G. d'Annunzio" University, Chieti-Pescara, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Antonucci
authors.affiliation: Paediatric Rheumatology Unit, Department of Paediatrics, "G. d'Annunzio" University, Chieti-Pescara, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Dadorante
authors.affiliation: Psycometric Laboratory, Department of Psychological, Humanities and Territorial Sciences, "G. d'Annunzio" University, Chieti-Pescara, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Balsamo
authors.affiliation: Laboratory of Molecular Genetics, Department of Psychological, Humanities and Territorial Sciences, "G. d'Annunzio" University, Chieti-Pescara, Italy.
authors.forename: Liborio
authors.initials: L
authors.lastname: Stuppia
authors.affiliation: Paediatric Rheumatology Unit, Department of Paediatrics, "G. d'Annunzio" University, Chieti-Pescara, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiarelli
authors.affiliation: Paediatric Rheumatology Unit, Department of Paediatrics, "G. d'Annunzio" University, Chieti-Pescara, Italy. Electronic address: luciana.breda@tin.it.
authors.forename: Luciana
authors.initials: L
authors.lastname: Breda
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha
keywords: Biological therapy; Gene polymorphisms; Juvenile idiopathic arthritis; Tumor necrosis factor-α