Lack of association of tumor necrosis factor-alpha gene polymorphisms with disease susceptibility and severity in Behçet's disease
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Although it has been reported that the MHC class I molecule, HLA-B51, is a risk factor for Behçet's disease (BD), contribution of the tumor necrosis factor (TNF) genes, which are located in the vicinity of the HLA-B locus, to the genetic susceptibility for BD has yet to be elucidated. The purpose of this study was to analyze the effect of TNF-α promoter polymorphisms at positions -308, -238 and -376 on the susceptibility, severity and clinical features of BD. The TNF-α gene sequences from 107 patients with BD and 102 healthy subjects were amplified by the polymerase chain reaction. Sequence analysis of the TNF-α gene locus, which contains promoter polymorphisms at positions -376, -308, and -238, was performed with a DNA sequencing kit on automated sequencer. The patients were classified according to disease severity and clinical features. Serum TNF-α level in the study groups was measured by sandwich enzyme immunoassay. In patients with BD the frequencies of TNF-α -308 (19.4% vs 18.4%), -238 (3.7% vs 5.9%), and -376 (0.9% vs 2.9%) gene polymorphisms were not found to be significantly different from those in healthy subjects. The TNF-α gene polymorphisms did not show any association with disease severity or clinical features. Serum TNF-α level was significantly higher in patients with BD than in healthy controls (3.10 ± 1.45 pg/ml vs 2.43 ± 1.94 pg/ml, P < 0.01). Serum TNF-α level was not found to be significantly associated with disease severity, activity, clinical findings and TNF-α genotypes. The results of this study suggest that the TNF-α gene polymorphisms are unlikely to play an important role in the pathogenesis and severity of BD. © Springer-Verlag 2005.
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