The significance of Toll-like receptor (TLR) 2 and 9 gene polymorphisms in psoriasis

The ethiopathogenesis of psoriasis is complex, multifactorial and still not well understood. Nowadays, the systemic, inflammatory and autoimmunological aspects of psoriasis are being emphasized [1].
Toll-like receptors (TLR) are characterized as pattern-recognition receptors, which are capable of potently activating various cell types. Toll-like receptors downstream signalling pathways lead to the production of a wide range of immune stimulatory cytokines and chemokines. Aberrant activation of TLR may result in an unrestricted inflammatory response, so the receptors may play a role in the development of inflammatory and autoimmune disorders [2].
TLR1, 2 and 5 are constitutively expressed on the normal keratinocytes [3]. TLR1 and TLR2 expression is further upregulated in psoriatic lesions [3, 4]. Seung et al. found a higher expression of TLR4 in guttate psoriasis compared to the plaque type and controls [5]. Moreover, TLR5 and TLR9 were upregulated by transforming growth factor  (TGF-) in psoriatic keratinocytes [6]. In another study, Begon et al. showed the expression of tumor necrosis factor  (TNF-) and interleukin (IL)-8 induced by the TLR2, 3 and 4 signalling pathway via nuclear factor B (NF-B) nuclear translocation in psoriatic keratinocytes [7].
In the light of these facts, TLR genes seem to be interesting gene candidates involved in psoriasis pathogenesis.
In this study we clarified the effect of Arg753Gln TLR2 and –1237 T/C TLR9 gene polymorphisms on the risk and the clinical manifestation of psoriasis.
The study group consisted of 175 unrelated patients with psoriasis vulgaris and 170 healthy, unrelated, age- and sex-matched volunteers. The mean Psoriasis Area Severity Index (PASI) was 16.9; PASI > 10 was observed in 90 patients. In the study group there were 121 (78.1%) patients with early onset (< 40 years) and 39 with late onset psoriasis (≥ 40 years). The gene polymorphisms were analyzed using the amplification refractory mutation system polymerase chain reaction method (ARMS-PCR).
There was no statistically significant association between genotype and allele frequencies in psoriatic patients in comparison with controls (Table 1). However, the presence of allele G in Arg753Gln TLR2 polymorphism was statistically more frequent in the group with late onset psoriasis in comparison with early onset psoriasis (100% vs. 96.2%; p = 0.0127). The presence of allele Tin –1237 T/C TLR9 polymorphism was more common...


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