Association of different tumor necrosis factor α promoter allele frequencies with ankylosing spondylitis in HLA-B27 positive individuals

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Abstract
Objective To investigate the potential association of tumor necrosis factor α (TNFα) 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 TNFα 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 wild‐type 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 TNFα promoter influence disease susceptibility in HLA‐B27 positive individuals. This protective effect of variant promoter alleles could be related to differences in TNFα production or could reflect the association of different B27 haplotypes with ankylosing spondylitis.