Objective: To investigate the potential association of tumor necrosis factor alpha (TNFalpha) promoter alleles with ankylosing spondylitis.
Methods: DNA from 141 HLA-B27 positive Caucasian patients with ankylosing spondylitis and 46 B27-positive and 99 B27-negative healthy Caucasian controls was investigated by polymerase chain reaction amplification of the TNFalpha promoter region and subsequent dot-blot analysis with allele-specific oligonucleotides.
Results: There was a significant decrease in the promoter alleles TNF-238.2 and TNF-308.2 in the ankylosing spondylitis group (266 wild-type alleles, 16 variant alleles) compared with the B27-positive (75 wildtype promoter alleles, 17 variant alleles; P<0.0004) and the B27-negative (159 wild-type promoter alleles, 39 variant alleles; P< 0.00001) control groups. Positivity for the variant promoter alleles conferred protection and a relative risk of 0.3 to B27-positive individuals.
Conclusion: These data indicate that allelic variations in the TNFalpha promoter influence disease susceptibility in HLA-B27 positive individuals. This protective effect of variant promoter alleles could be related to differences in TNFalpha production or could reflect the association of different B27 haplotypes with ankylosing spondylitis.