The -308.1 polymorphism in the promoter region of the tumor necrosis factor gene is associated with ankylosing spondylitis independent of HLA-B27

Objective. To investigate the allele frequencies of 6 polymorphic sites spa nning the region of the genome close to the tumor necrosis factor (TNF) gen e in a group of HLA-B27 positive patients with ankylosing spondylitis (AS) in the West of Scotland. Methods. One hundred sixty-seven patients with AS, 93 healthy controls, and 88 HLA-B27 positive healthy controls, all from the West of Scotland, were typed by polymerase chain reaction (PCR) for 3 restriction fragment length polymorphisms (RFLP) and 3 microsatellite polymorphic sites spanning the TN F gene cluster. The distribution of these alleles was correlated with the p resence of extraspinal manifestations such as peripheral joint disease and uveitis. Results. The frequency of the Nco-1.2 allele was significantly reduced in p atients compared to the genetically unselected control population (p < 0.05 ), but was no different from the MLA-B27 positive controls. However, the -3 08.1 allele was significantly increased in the patients compared to the HLA -B27 positive controls (p < 0.03). Conclusion. This study confirms the importance of correct matching in genet ic analysis in disease association studies, and provides further evidence s upporting the involvement of genes other than the MHC class I locus in the pathogenesis and features of AS.