The novel -G646A polymorphism of the TNFalpha promoter is associated with the HLA-B51 allele in Korean patients with Behçet's disease.

OBJECTIVE

This study was performed to examine the influence of tumour necrosis factor-alpha (TNFalpha) promoter polymorphisms on disease susceptibility and clinical features of Behçet's disease (BD) and the association between TNFalpha polymorphisms and human leucocyte antigen (HLA)-B51.

METHODS

We examined 115 patients with BD and 114 healthy subjects. Six single nucleotide polymorphisms (SNPs) of the TNFalpha promoter at positions -1031, -863, -857, -308, -238, and -646 were analysed using automated sequencing. We compared the frequencies of alleles and genotypes in patients with BD and controls using the chi(2)-test or Fisher's exact test. Haplotype frequency was also assessed using the chi(2)-test.

RESULTS

We found no significant differences in the frequencies of polymorphic genotypes and alleles of the TNFalpha promoter region between BD patients and controls. The resulting haplotype frequencies of the BD patients were also not significantly different from those of controls. None of the TNFalpha promoter polymorphisms analysed here were associated with clinical features. Patients with the novel -646A allele of the TNFalpha promoter region were significantly associated with the expression of the HLA-B51 allele (p(corr) = 0.006), although this novel polymorphic allele was not associated with BD susceptibility.

CONCLUSION

The novel -646A TNFalpha allele was associated with the expression of HLA-B51 in Korean BD, although we found no genetic role of TNFalpha promoter polymorphisms in the susceptibility to BD. Further studies to examine the contributions of this gene polymorphism and HLA-B51 to the susceptibility to BD in large populations are required.