Association of different tumor necrosis factor alpha promoter allele frequencies with ankylosing spondylitis in HLA-B27 positive individuals.
OBJECTIVE
To investigate the potential association of tumor necrosis factor alpha (TNFalpha) 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 TNFalpha 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 wildtype 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.


CONCLUSIONS
These data indicate that allelic variations in the TNFalpha promoter influence disease susceptibility in HLA-B27 positive individuals. This protective effect of variant promoter alleles could be related to differences in TNFalpha production or could reflect the association of different B27 haplotypes with ankylosing spondylitis.
Johannes Gutenberg Universität Mainz, Germany.
T
T
Höhler
T
T
Schäper
P M
PM
Schneider
K H
KH
Meyer zum Büschenfelde
E
E
Märker-Hermann
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics; D015796:HLA-B27 Antigen / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015796:HLA-B27 Antigen; D014409:Tumor Necrosis Factor-alpha