BACKGROUND: Cytokine production is under genetic control, and certain allelic variants of cytokine genes are associated with higher or lower cytokine production in vitro and in vivo. Psoriasis is associated with an overexpression in the involved skin of T-helper cell type 1 (Th1) cytokines, e.g. interferon (IFN) -gamma and tumour necrosis factor (TNF) alpha and relative underexpression of Th2 cytokines, e.g. interleukin (IL) -4 and IL-10. Objective We investigated the hypothesis that allelic variants of genes for a high production of Th1 cytokines or TNF-alpha, or conversely low production of Th2 cytokines might represent a risk factor for developing psoriasis. METHODS: Genotyping for IFN-gamma, IL-10, IL-4 and TNF-alpha was undertaken for 84 patients with psoriasis and compared with control data on file. RESULTS: Genotype frequencies showed no differences between patients and controls for IFN-gamma, TNF-alpha or IL-4. For IL-10, patients with late onset psoriasis (over 40 years) were more likely to be heterozygous at position - 1082 (P = 0.02), corresponding to intermediate production of IL-10 in vitro and in vivo. CONCLUSIONS: Psoriasis is not determined by a genotype consistent with high production of Th1 cytokines or low production of Th2 cytokines. Thus, the Th1 cytokine profile found in psoriatic plaques is most likely a consequence of local factors.
BACKGROUND: Cytokine production is under genetic control, and certain allelic variants of cytokine genes are associated with higher or lower cytokine production in vitro and in vivo. Psoriasis is associated with an overexpression in the involved skin of T-helper cell type 1 (Th1) cytokines, e.g. interferon (IFN) -gamma and tumour necrosis factor (TNF) alpha and relative underexpression of Th2 cytokines, e.g. interleukin (IL) -4 and IL-10. Objective We investigated the hypothesis that allelic variants of genes for a high production of Th1 cytokines or TNF-alpha, or conversely low production of Th2 cytokines might represent a risk factor for developing psoriasis. METHODS: Genotyping for IFN-gamma, IL-10, IL-4 and TNF-alpha was undertaken for 84 patients with psoriasis and compared with control data on file. RESULTS: Genotype frequencies showed no differences between patients and controls for IFN-gamma, TNF-alpha or IL-4. For IL-10, patients with late onset psoriasis (over 40 years) were more likely to be heterozygous at position - 1082 (P = 0.02), corresponding to intermediate production of IL-10 in vitro and in vivo. CONCLUSIONS:Psoriasis is not determined by a genotype consistent with high production of Th1 cytokines or low production of Th2 cytokines. Thus, the Th1 cytokine profile found in psoriatic plaques is most likely a consequence of local factors.
Authors: Najl V Valeyev; Christian Hundhausen; Yoshinori Umezawa; Nikolay V Kotov; Gareth Williams; Alex Clop; Crysanthi Ainali; Christos Ouzounis; Sophia Tsoka; Frank O Nestle Journal: PLoS Comput Biol Date: 2010-12-02 Impact factor: 4.475