Polymorphism within the tumor necrosis factor alpha (TNF) promoter region in patients with ankylosing spondylitis

In addition to HLA-B27, other genetic factors are thought to be involved in the pathogenesis of ankylosing spondylitis (AS). Because of the location o f the TNF gene in the vicinity of the HLA-B locus, and the prominent role i n inflammation of its produce, we investigated the association between BS a nd two G to A transition polymorphisms located at position -238 and -376 in the promoter region of the TNF gene. The distribution of the TNF alleles w as determined in 86 HLA-B27+ AS patients and 163 healthy controls. From the 86 AS patients, 33 suffered from acute anterior uveitis (AAU). No signific ant difference for the TNF-376 polymorphism in AS and healthy controls was observed. The frequency of the TNF-238A allele in HLA-B27(+) AS patients wa s significantly decreased compared to random controls (p = 0.021). However, the frequency of the TNF-238A allele in HLA-B27(+) AS patients was not sig nificantly different from chat observed in HLA-B27(+) healthy individuals ( p = 0.6). Assessment of association showed that the TNF-238G allele is in l inkage disequilibrium with the HLA-B27 allele (Delta = 0.051; P = 0.008). T herefore, we conclude that the association between TNF-238G and AS is secon dary to the HLA-B27 gene and that TNF-238 and TNF-376 alleles are nor likel y to be involved in the susceptibility to AS. Human Immunology 60, 140-144 (1999). (C) American Society for Histocompatibility and Immunogenetics, 199 9. Published by Elsevier Science Inc.