W. Kaluza et al., Different transcriptional activity and in vitro TNF-alpha production in psoriasis patients carrying the TNF-alpha 238A promoter polymorphism, J INVES DER, 114(6), 2000, pp. 1180-1183
Genes encoded on chromosome 6 within the major histocompatibility complex r
egion are thought to play an important role in the pathogenesis of psoriasi
s. A potential candidate gene is tumor necrosis factor alpha. The tumor nec
rosis factor alpha promoter contains several polymorphisms including two G-
->A transitions at position -308 and -238, which are the most common in Cau
casian populations. The TNF238.2 (-238A) allele has been strongly associate
d with psoriasis. We have investigated the effect of the -238 and -308 vari
ants on transcription of the tumor necrosis factor alpha gene in luciferase
reporter gene assays. In addition, peripheral blood mononuclear cells of 4
7 patients with psoriasis and 43 controls were stimulated with different an
tigens and mitogens (streptococcal sonicate and superantigen, lipopolysacch
aride, phorbol-12-myristate, phytohemagglutinin, CD3 antibodies) and tumor
necrosis factor alpha production was measured in supernatants by enzyme-lin
ked immunosorbent assay. The psoriasis-associated tumor necrosis factor alp
ha promoter allele TNF238.2 showed a significantly decreased transcriptiona
l activity. Peripheral blood mononuclear cells carrying this allele produce
d significantly less tumor necrosis factor alpha after stimulation with T c
ell mitogens and streptococcal antigens in comparison to controls. The prom
oter allele TNF238.2 seems to influence tumor necrosis factor alpha product
ion; a possible role in the pathogenesis of psoriasis has to be further eva
luated.