Tumor Necrosis Factor-α −308 Genotypes Influence Inflammatory Activity and TNF-α Serum Concentrations in Children with Juvenile Idiopathic Arthritis

Mourão, Ana Filipa; Caetano-Lopes, Joana; Costa, Patrícia; Canhão, Helena; Santos, María José; Pinto, Patrícia; Brito, Iva; Nicola, Paulo; Cavaleiro, João; Teles, José; Sousa, Artur; Gomes, José Melo; Branco, Jaime; Costa, José; Pedro, J. Branco; Queiróz, M Viana; Fonseca, João Eurico

doi:10.3899/jrheum.080615

Cited by 24 publications

(16 citation statements)

References 30 publications

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“…Of interest, we found higher, though not signiWcantly, serum TNF levels in SLE patients carrying the A allele, which may have contributed to the observed higher disease activity and greater prevalence of lupus nephritis. These results are in accordance with previous studies of Portuguese patients with inXammatory rheumatic diseases, which found the TNF promoter polymorphism at position -308 to inXuence rheumatoid arthritis activity and severity [26], juvenile idiopathic arthritis inXammatory activity [27], and also some clinical features of ankylosing spondylitis [28], but not to inXuence the susceptibility to these diseases. The contribution of the LTA gene polymorphism at position 252 to SLE susceptibility has been reported mainly in Asian populations [12][13][14].…”

Section: Was Reported In European Patients With Sle and A Meta-analyssupporting

confidence: 94%

TNF promoter -308 G>A and LTA 252 A>G polymorphisms in Portuguese patients with systemic lupus erythematosus

et al. 2011

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The polymorphism of the tumor necrosis factor (TNF) promoter gene at position -308 and that of the lymphotoxin alpha (LTA) gene at position 252 have been implicated as genetic risk factors for systemic lupus erythematosus (SLE) in some populations. In a nested case-control study, we investigated the possible association of these polymorphisms with susceptibility to SLE and with phenotypic disease features in Portuguese Caucasian patients. TNF-308 G>A and LTA 252 A>G polymorphisms were determined by restriction fragment length polymorphism analysis in a cohort of 115 SLE patients and 152 unrelated healthy controls, and the magnitude of the association between genotypes and SLE diagnosis was calculated. For SLE patients, we also tested the association between disease characteristics and genotypes. No significant differences in genotype or allele frequencies could be identified between SLE cases and controls. Lupus nephritis (OR = 2.84; 95%CI 1.14-7.03, P = 0.02) and the presence of anti-Sm antibodies (OR = 3.11; 95%CI 1.08-8.94; P = 0.03) were significantly more prevalent among lupus patients possessing the TNF-308 A allele. The occurrence of nephritis was also higher in LTA 252 G allele carriers (OR = 2.90; 95%CI 1.12-7.54; P = 0.02). Our results do not support a major role of either the TNF-308 G>A or the LTA 252 A>G polymorphisms as genetic risk factors for SLE. Nevertheless, these polymorphisms appear to associate with the risk of renal lupus and distinct immunological features.

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Section: Was Reported In European Patients With Sle and A Meta-analyssupporting

confidence: 94%

TNF promoter -308 G>A and LTA 252 A>G polymorphisms in Portuguese patients with systemic lupus erythematosus

et al. 2011

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“…Follow-up ranged from 6 months to as much as 23 years. In total, 6 out of 15 studies were prospective cohort studies36 43–45 49 50 and one was a cross-sectional study,51 which assessed genetic predictors only.…”

Section: Resultsmentioning

confidence: 99%

Early predictors of prognosis in juvenile idiopathic arthritis: a systematic literature review

Dijkhuizen

Wulffraat

2014

Ann Rheum Dis

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“…Several studies have focused blood and synovial cytokine polymorphisms; a major involved cytokine in JIA is the TNF- α ; the polymorphisms of its gene have been evaluated in different studies to establish its role in the pathogenesis and in the therapeutic response to anti-TNF- α drugs [4, 6, 7, 35, 36]. …”

Section: Resultsmentioning

confidence: 99%

“…The role of −308A/G polymorphism in JIA was investigated in many studies. Some authors found that the A allele was significantly more frequent in JIA subjects with respect to controls and was related to a higher disease activity [36] and a poor prognosis [43, 74]. Zeggini et al showed that the TNF −308A allele is more frequently found in rheumatoid factor positive juvenile polyarthritis and is associated with a more severe disease, while the more common TNF −308G allele may be protective [13].…”

Section: Resultsmentioning

confidence: 99%

TNF-αPolymorphisms in Juvenile Idiopathic Arthritis: Which Potential Clinical Implications?

Sereno

Breda

Laganà

et al. 2012

International Journal of Rheumatology

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Whether tumor necrosis factor alpha (TNF-α) gene polymorphisms (SNPs) influence disease susceptibility and treatment of patients with juvenile idiopathic arthritis (JIA) is presently uncertain. TNF-α is one of the most important cytokine involved in JIA pathogenesis. Several single nucleotide polymorphisms (SNPs) have been identified within the region of the TNF-α gene but only a very small minority have proven functional consequences and have been associated with susceptibility to JIA. An association between some TNF-α SNPs and adult rheumatoid arthritis (RA) susceptibility, severity and clinical response to anti-TNF-α treatment has been reported. The most frenquetly studied TNF-α SNP is located at −308 position, where a substitution of the G allele with the rare A allele has been found. The presence of the allele −308A is associated to JIA and to a poor prognosis. Besides, the −308G genotype has been associated with a better response to anti-TNF-α therapy in JIA patients, confirming adult data. Psoriatic and oligoarticular arthritis are significantly associated to the −238 SNP only in some works. Studies considering other SNPs are conflicting and inconclusive. Large scale studies are required to define the contribution of TNF-α gene products to disease pathogenesis and anti-TNF-α therapeutic efficacy in JIA.

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Tumor Necrosis Factor-α −308 Genotypes Influence Inflammatory Activity and TNF-α Serum Concentrations in Children with Juvenile Idiopathic Arthritis

Abstract: 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.

Cited by 24 publications

References 30 publications

TNF promoter -308 G>A and LTA 252 A>G polymorphisms in Portuguese patients with systemic lupus erythematosus

TNF promoter -308 G>A and LTA 252 A>G polymorphisms in Portuguese patients with systemic lupus erythematosus

Early predictors of prognosis in juvenile idiopathic arthritis: a systematic literature review

TNF-αPolymorphisms in Juvenile Idiopathic Arthritis: Which Potential Clinical Implications?

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