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 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).


CONCLUSIONS
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.
McGarry
F
F
Centre for Rheumatic Diseases, University Department of Medicine, Glasgow Royal Infirmary, Scotland.
Walker
R
R
Sturrock
R
R
Field
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D005787:Gene Frequency; D005819:Genetic Markers; D015796:HLA-B27 Antigen; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D005819:Genetic Markers; D015796:HLA-B27 Antigen; D014409:Tumor Necrosis Factor-alpha