title: Tumor necrosis factor-alpha -308 genotypes influence inflammatory activity and TNF-alpha serum concentrations in children with juvenile idiopathic arthritis.
abstract: OBJECTIVE
  Considering the relevance of tumor necrosis factor-alpha (TNF-alpha) in the pathophysiology of juvenile idiopathic arthritis (JIA), it is likely that polymorphisms in its promoter area may be relevant in disease susceptibility and activity. We investigated if clinical measures of JIA activity and TNF-alpha serum concentrations were associated with TNF-alpha -308 genotypes.
  
  
  METHODS
  Portuguese patients with JIA in 5 pediatric rheumatology centers were recruited consecutively, along with a control group of healthy subjects. Demographic and clinical data and blood samples were collected from each patient. DNA was extracted for analysis of TNF-alpha gene promoter polymorphisms at position -308 by restriction fragment-length polymorphism.
  
  
  RESULTS
  One hundred fourteen patients and 117 controls were evaluated; 57% of patients presented the oligoarticular subtype, 25% the polyarticular subtype, 8% the systemic subtype, and 9% had enthesitis-related arthritis and 5% psoriatic arthritis. Twenty-four percent of the patients presented the -308 GA/AA genotypes and 76% the -308 GG genotype, similar to findings in controls. Patients with the -308 GA/AA genotype had higher degree of functional impairment, erythrocyte sedimentation rate, 100-mm visual analog scale score for disease activity, and TNF-alpha levels compared to those with the -308 GG genotype.
  
  
  CONCLUSIONS
  TNF-alpha -308 GA/AA genotypes were found to be related to higher inflammatory activity and worse measures of disease activity in Portuguese patients with JIA. They were not associated with susceptibility to JIA.
authors.affiliation: Rheumatology Research Unit, Instituto de Medicina Molecular, Edifício Egas Moniz, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal.
authors.forename: Ana Filipa
authors.initials: AF
authors.lastname: Mourão
authors.forename: Joana
authors.initials: J
authors.lastname: Caetano-Lopes
authors.forename: Paula
authors.initials: P
authors.lastname: Costa
authors.forename: Helena
authors.initials: H
authors.lastname: Canhão
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Santos
authors.forename: Patrícia
authors.initials: P
authors.lastname: Pinto
authors.forename: Iva
authors.initials: I
authors.lastname: Brito
authors.forename: Paulo
authors.initials: P
authors.lastname: Nicola
authors.forename: João
authors.initials: J
authors.lastname: Cavaleiro
authors.forename: José
authors.initials: J
authors.lastname: Teles
authors.forename: Artur
authors.initials: A
authors.lastname: Sousa
authors.forename: José Melo
authors.initials: JM
authors.lastname: Gomes
authors.forename: Jaime
authors.initials: J
authors.lastname: Branco
authors.forename: José Teixeira
authors.initials: JT
authors.lastname: da Costa
authors.forename: João Gomes
authors.initials: JG
authors.lastname: Pedro
authors.forename: Mário Viana
authors.initials: MV
authors.lastname: de Queiroz
authors.forename: João Eurico
authors.initials: JE
authors.lastname: Fonseca
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000097:blood / Q000235:genetics; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D011401:Promoter Regions, Genetic / Q000235:genetics; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
chemical_list: D014409:Tumor Necrosis Factor-alpha