The -308 polymorphism in the tumour necrosis factor (TNF) gene promoter region and ex vivo lipopolysaccharide-induced TNF expression and cytotoxic activity in Chilean patients with rheumatoid arthritis.
OBJECTIVE
To investigate the association of the -308 polymorphism in the promoter region of the tumour necrosis factor (TNF) gene with susceptibility to the development of RA. We also explored the expression and cytotoxicity of TNF in relation to the -308 polymorphism.


METHODS
We recruited 92 RA patients and 42 healthy control subjects. Genotyping for the TNF promoter was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. To study the overexpression of TNF we used a whole-blood culture system. TNF cytotoxicity was assessed in the L929 cell line.


RESULTS
The TNF2 allele was found in 23% of RA patients and 10% of controls. Although both groups showed high variability in serum TNF concentration, in the lipopolysaccharide-induced TNF level and in the cytotoxicity of the cytokine in the L929 cell line, these differences were not associated with the -308 TNF polymorphism.


CONCLUSIONS
No associations were found between the -308 TNF promoter polymorphism, serum and ex vivo TNF levels and the cytotoxic activity of TNF in RA patients.
Cuenca
J
J
Disciplinary Program of Immunology, Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, Chile.
Cuchacovich
M
M
Pérez
C
C
Ferreira
L
L
Aguirre
A
A
Schiattino
I
I
Soto
L
L
Cruzat
A
A
Salazar-Onfray
F
F
Aguillón
J C
JC
D000328:Adult; D000368:Aged; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000235:genetics*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha