Browsing by Author "Silm, Helgi"

Background Interleukin (IL) 19, IL-20 and IL-24 belong to the IL-10 cytokine family and have been identified to play a role in the regulation of epidermal functions and in inflammation. The genes encoding IL-19, IL-20 and IL-24 are located within a gene cluster on chromosome 1q31-32 and carry frequent genetic variations. Objectives This study investigated whether variations in the IL19, IL20 and IL24 genes that have previously been associated with plaque-type psoriasis may also play a role in palmoplantar pustulosis (PPP). Patients Fifteen polymorphisms were analysed in 43 patients with PPP and in 149 healthy control subjects. Results The rare allele of IL20 1380 A -> G (rs2981573) was less frequent in patients with PPP compared with healthy controls (OR 1.95, 95% CI 1.00-3.79). Haplotype analyses of IL19 and IL20 suggested an increased risk for PPP associated with IL20 haplotype GAA (OR 2.39, 95% CI 1.17-4.86) and a reduced risk for PPP associated both with IL19 haplotype GATGATA (OR 0.41, 95% CI 0.16-1.05) and IL20 haplotype GGG (OR 0.48, 95% CI 0.23-0.98). Extended haplotype analysis revealed an association of IL19/IL20 haplotype GACACCGGAA with a higher risk for PPP (OR 2.31, 95% CI 1.05-5.10) and of IL20/IL24 haplotype CAAAC with a reduced risk for PPP (OR 0.12, 95% CI 0.02-0.82). Conclusion This exploratory study supports the hypothesis that variations of genes of the IL-19 subfamily of cytokines influence susceptibility to PPP. However, due to the limited size of the study samples, this current concept should be considered as preliminary and the results need to be confirmed in future independent studies.

The interleukin-20-receptor I complex (IL-20-RI) is composed of two chains, IL20RA and IL20RB. Its ligands are the three members of the IL19 subfamily of cytokines, IL-19, IL-20 and IL-24. These cytokines are important in the manifestation of psoriatic lesions and, recently, an association of polymorphisms of IL20 with psoriasis has been described. In the present study we tested the hypotheses that genetic variations of the IL-20-RI influence susceptibility to psoriasis and investigated single nucleotide polymorphisms (SNPs) in the IL20RA and IL20RB genes in psoriasis patients (n = 254) and healthy controls (n 224). We found no association of any of the investigated SNPs with the disease. Analysis of pairwise linkage disequilibrium (LD) across studied markers revealed a strong level of LD between SNPs within the IL20RA gene and SNPs within the IL20RB gene, and, for both genes six common haplotypes were identified with an estimated frequency >= 1%. Haplotype analyses suggested that the IL20RA haplotype CCG (rs1184860, rs1167846, rs1167849) is significantly associated with psoriasis (OR 3.14, 95% CI 1.61-6.14), whereas the TTG haplotype had a protective effect (OR 0.20, 95% CI 0.07-0.55). The risk haplotype defining SNPs 1167846 and 1184860 were found to modify paired box 5 and homeobox A9 sites, respectively, two transcription factors related to the differentiation of immune cells. Further studies are needed to confirm the genetic association and to investigate the functional relevance of IL20RA haplotypes in psoriasis.