title: TNF-alpha promoter gene polymorphisms in Spanish children with persistent oligoarticular and systemic-onset juvenile idiopathic arthritis.
abstract: OBJECTIVE
  To explore the possible association/s of the first reported tumour necrosis factor (TNF-alphaTNF-) alpha promoter gene polymorphisms -308, -238, -376 and -163 (G-->A) with systemic (SoJIA) and oligoarticular subtypes of juvenile idiopathic arthritis (JIA); and to test the association between these polymorphisms and the class I/class II HLA alleles in our population.
  
  
  METHODS
  The patient group comprised 29 oligoarticular and 26 systemic Caucasian Spanish children with JIA; 68 healthy volunteers from the same ethnic group and geographical region served as controls. HLA alleles were determined using low-resolution polymerase chain reaction (PCR). TNF-alpha promoter gene polymorphisms were screened using PCR denaturing gradient gel electrophoresis (PCR-DGGE), followed, if positive, by restriction fragment length polymorphism (RFLP) analysis for identification.
  
  
  RESULTS
  No statistical association was found between the four polymorphisms studied and JIA. However, the -308 G-->A polymorphism (TNF A2) tended to be more frequent in patients with SoJIA than in the oligoarticular group. TNF A2 was strongly associated with the extended haplotype A1B8DR3 (p = 0.003), and the tandem polymorphism -238/-376 in the presence of B18 and DR3.
  
  
  CONCLUSIONS
  The TNF A2 allele was more frequent in SoJIA than in the oligoarticular group. TNF A2 can help to create a more inflammatory milieu in this JIA subtype, in combination with other polymorphisms involved in regulatory sequences of key molecules in the inflammatory response. The association of the -308 and -238/-376 polymorphisms with specific alleles of the HLA is reconfirmed.
authors.affiliation: Rheumatology Department, Hospital Valle de Hebrón, Barcelona, Spain. cmodesto60@yahoo.es
authors.forename: C
authors.initials: C
authors.lastname: Modesto
authors.forename: A
authors.initials: A
authors.lastname: Patiño-García
authors.forename: E
authors.initials: E
authors.lastname: Sotillo-Piñeiro
authors.forename: J
authors.initials: J
authors.lastname: Merino
authors.forename: J
authors.initials: J
authors.lastname: García-Consuegra
authors.forename: R
authors.initials: R
authors.lastname: Merino
authors.forename: M J
authors.initials: MJ
authors.lastname: Rua
authors.forename: L
authors.initials: L
authors.lastname: Sierrasesúmaga
authors.forename: C
authors.initials: C
authors.lastname: Arnal
mesh_terms: D001171:Arthritis, Juvenile / Q000208:ethnology / Q000235:genetics*; D002648:Child; D016001:Confidence Intervals; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D013030:Spain / Q000208:ethnology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha