Tumor necrosis factor-alpha -308 genotypes influence inflammatory activity and TNF-alpha serum concentrations in children with juvenile idiopathic arthritis.
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.
Mourão
Ana Filipa
AF
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.
Caetano-Lopes
Joana
J
Costa
Paula
P
Canhão
Helena
H
Santos
Maria José
MJ
Pinto
Patrícia
P
Brito
Iva
I
Nicola
Paulo
P
Cavaleiro
João
J
Teles
José
J
Sousa
Artur
A
Gomes
José Melo
JM
Branco
Jaime
J
da Costa
José Teixeira
JT
Pedro
João Gomes
JG
de Queiroz
Mário Viana
MV
Fonseca
João Eurico
JE
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
D014409:Tumor Necrosis Factor-alpha