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

J Rheumatol. 1999 May;26(5):1110-6.


Objective: To investigate the allele frequencies of 6 polymorphic sites spanning the region of the genome close to the tumor necrosis factor (TNF) gene 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 TNF gene cluster. The distribution of these alleles was correlated with the presence of extraspinal manifestations such as peripheral joint disease and uveitis.

Results: The frequency of the Nco-1.2 allele was significantly reduced in patients compared to the genetically unselected control population (p < 0.05), but was no different from the HLA-B27 positive controls. However, the -308.1 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 genetic analysis in disease association studies, and provides further evidence supporting the involvement of genes other than the MHC class I locus in the pathogenesis and features of AS.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Gene Frequency
  • Genetic Markers
  • HLA-B27 Antigen*
  • Humans
  • Microsatellite Repeats / genetics
  • Middle Aged
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Promoter Regions, Genetic*
  • Spondylitis, Ankylosing / genetics*
  • Spondylitis, Ankylosing / immunology
  • Tumor Necrosis Factor-alpha / genetics*


  • Genetic Markers
  • HLA-B27 Antigen
  • Tumor Necrosis Factor-alpha