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  • Title: Tumor necrosis factor alpha promoter polymorphisms in patients with juvenile idiopathic arthritis.
    Author: Schmeling H, Wagner U, Peterson A, Horneff G.
    Journal: Clin Exp Rheumatol; 2006; 24(1):103-8. PubMed ID: 16539828.
    Abstract:
    OBJECTIVE: To investigate the potential association of tumor necrosis factor-alpha (TNF) promoter alleles within subtypes of juvenile idiopathic arthritis (JIA) compared to healthy controls in a Caucasian population. METHODS: TNF-alpha promoter polymorphisms at positions -163, -238, -244, -308, -376 were determined in 228 patients with JIA and 196 healthy individuals. Genomic DNA was isolated and a PCR fragment of about 500 base pairs of the TNF gene promoter were amplified by PCR. Detection of polymorphisms was achieved by a single sequencing procedure. RESULTS: The TNF -238A allele was more frequent in the psoriatic arthritis JIA subgroup compared to healthy controls as well as to non-psoriatic JIA patients (p < 0.001, chi-square-test) and was associated with the more frequent occurrence of joint erosion (p < 0.05, chi-square-test). The frequency of the TNF -308A allele was significantly lower in patients with rheumatoid factor negative polyarthritis JIA patients compared to healthy controls, respectively (p < 0.05, chi-square-test). Joint erosions were detectable more often in rheumatoid factor negative polyarthritis JIA patients with the G/A genotype (80%) than in those with the G/G genotype (45%) (p = 0.20). The rare alleles at position -376 or at positions -163 and -244 were found very infrequently. CONCLUSION: TNF promoter polymorphisms may play a role in the pathogenesis of JIA. The TNF-238A allele seems to be associated with juvenile psoriatic arthritis. The TNF-308A allele is less frequently found in rheumatoid factor negative but not in rheumatoid factor positive polyarthritis and may therefore be associated with a more severe disease, while the more common TNF-308G allele may be protective.
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