Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Association analysis of IL20RA and IL20RB genes in psoriasis

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Gallagher G, Eskdale J, Jordan W, Peat J, Campbell J, Boniotto M et al. Human interleukin-19 and its receptor: a potential role in the induction of Th2 responses. Int Immunopharmacol 2004; 4: 615–626.

    Article  CAS  Google Scholar 

  2. Blumberg H, Conklin D, Xu WF, Grossmann A, Brender T, Carollo S et al. Interleukin 20: discovery, receptor identification, and role in epidermal function. Cell 2001; 104: 9–19.

    Article  CAS  Google Scholar 

  3. Chang C, Magracheva E, Kozlov S, Fong S, Tobin G, Kotenko S et al. Crystal structure of interleukin-19 defines a new subfamily of helical cytokines. J Biol Chem 2003; 278: 3308–3313.

    Article  CAS  Google Scholar 

  4. Sabat R, Wallace E, Endesfelder S, Wolk K . IL-19 and IL-20: two novel cytokines with importance in inflammatory diseases. Expert Opin Ther Targets 2007; 11: 601–612.

    Article  CAS  Google Scholar 

  5. Sa SM, Valdez PA, Wu J, Jung K, Zhong F, Hall L et al. The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis. J Immunol 2007; 178: 2229–2240.

    Article  CAS  Google Scholar 

  6. Boniface K, Lecron JC, Bernard FX, Dagregorio G, Guillet G, Nau F et al. Keratinocytes as targets for interleukin-10-related cytokines: a putative role in the pathogenesis of psoriasis. Eur Cytokine Netw 2005; 16: 309–319.

    CAS  PubMed  Google Scholar 

  7. Romer J, Hasselager E, Norby PL, Steiniche T, Thorn Clausen J, Kragballe K . Epidermal overexpression of interleukin-19 and -20 mRNA in psoriatic skin disappears after short-term treatment with cyclosporine a or calcipotriol. J Invest Dermatol 2003; 121: 1306–1311.

    Article  CAS  Google Scholar 

  8. Otkjaer K, Kragballe K, Funding AT, Clausen JT, Noerby PL, Steiniche T et al. The dynamics of gene expression of interleukin-19 and interleukin-20 and their receptors in psoriasis. Br J Dermatol 2005; 153: 911–918.

    Article  CAS  Google Scholar 

  9. Wolk K, Kunz S, Asadullah K, Sabat R . Cutting edge: immune cells as sources and targets of the IL-10 family members? J Immunol 2002; 168: 5397–5402.

    Article  CAS  Google Scholar 

  10. Wei CC, Chen WY, Wang YC, Chen PJ, Lee JY, Wong TW et al. Detection of IL-20 and its receptors on psoriatic skin. Clin Immunol 2005; 117: 65–72.

    Article  CAS  Google Scholar 

  11. Kunz S, Wolk K, Witte E, Witte K, Doecke WD, Volk HD et al. Interleukin (IL)-19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs. Exp Dermatol 2006; 15: 991–1004.

    Article  CAS  Google Scholar 

  12. Wolk K, Witte E, Wallace E, Docke WD, Kunz S, Asadullah K et al. IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 2006; 36: 1309–1323.

    Article  CAS  Google Scholar 

  13. Boniface K, Bernard FX, Garcia M, Gurney AL, Lecron JC, Morel F . IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes. J Immunol 2005; 174: 3695–3702.

    Article  CAS  Google Scholar 

  14. Li HH, Lin YC, Chen PJ, Hsiao CH, Lee JY, Chen WC et al. Interleukin-19 upregulates keratinocyte growth factor and is associated with psoriasis. Br J Dermatol 2005; 153: 591–595.

    Article  CAS  Google Scholar 

  15. Kingo K, Kõks S, Nikopensius T, Silm H, Vasar E . Polymorphisms in the interleukin-20 gene: relationships to plaque-type psoriasis. Genes Immun 2004; 5: 117–121.

    Article  CAS  Google Scholar 

  16. Kõks S, Kingo K, Rätsep R, Karelson M, Silm H, Vasar E . Combined haplotype analysis of the interleukin-19 and -20 genes: relationship to plaque-type psoriasis. Genes Immun 2004; 5: 662–667.

    Article  Google Scholar 

  17. Kõks S, Kingo K, Vabrit K, Rätsep R, Karelson M, Silm H et al. Possible relations between the polymorphisms of the cytokines IL-19, IL-20 and IL-24 and plaque-type psoriasis. Genes Immun 2005; 6: 407–415.

    Article  Google Scholar 

  18. Kingo K, Mossner R, Koks S, Ratsep R, Kruger U, Vasar E et al. Association analysis of IL19, IL20 and IL24 genes in palmoplantar pustulosis. Br J Dermatol 2007 156: 646–652.

    Article  CAS  Google Scholar 

  19. Dumoutier L, Leemans C, Lejeune D, Kotenko SV, Renauld JC . Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types. J Immunol 2001; 167: 3545–3549.

    Article  CAS  Google Scholar 

  20. Donnelly RP, Sheikh F, Kotenko SV, Dickensheets H . The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain. J Leukoc Biol 2004; 76: 314–321.

    Article  CAS  Google Scholar 

  21. Pletnev S, Magracheva E, Kozlov S, Tobin G, Kotenko SV, Wlodawer A et al. Characterization of the recombinant extracellular domains of human interleukin-20 receptors and their complexes with interleukin-19 and interleukin-20. Biochemistry 2003; 42: 12617–12624.

    Article  CAS  Google Scholar 

  22. Parrish-Novak J, Xu W, Brender T, Yao L, Jones C, West J et al. Interleukins 19, 20, and 24 signal through two distinct receptor complexes. Differences in receptor-ligand interactions mediate unique biological functions. J Biol Chem 2002; 277: 47517–47523.

    Article  CAS  Google Scholar 

  23. Wang F, Lee E, Lowes MA, Haider AS, Fuentes-Duculan J, Abello MV et al. Prominent production of IL-20 by CD68+/CD11c+ myeloid-derived cells in psoriasis: gene regulation and cellular effects. J Invest Dermatol 2006; 126: 1590–1599.

    Article  CAS  Google Scholar 

  24. Tzankov AS, Went PT, Munst S, Papadopoulos T, Jundt G, Dirnhofer SR . Rare expression of BSAP (PAX-5) in mature T-cell lymphomas. Mod Pathol 2007; 20: 632–637.

    Article  CAS  Google Scholar 

  25. Friedman AD . Transcriptional control of granulocyte and monocyte development. Oncogene 2007; 26: 6816–6828.

    Article  CAS  Google Scholar 

  26. Cobaleda C, Jochum W, Busslinger M . Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors. Nature 2007; 449: 473–477.

    Article  CAS  Google Scholar 

  27. Lohoff M, Mittrucker HW, Prechtl S, Bischof S, Sommer F, Kock S et al. Dysregulated T helper cell differentiation in the absence of interferon regulatory factor 4. Proc Natl Acad Sci USA 2002; 99: 11808–11812.

    Article  CAS  Google Scholar 

  28. Klein U, Casola S, Cattoretti G, Shen Q, Lia M, Mo T et al. Transcription factor IRF4 controls plasma cell differentiation and class-switch recombination. Nat Immunol 2006; 7: 773–782.

    Article  CAS  Google Scholar 

  29. Sciammas R, Shaffer AL, Schatz JH, Zhao H, Staudt LM, Singh H . Graded expression of interferon regulatory factor-4 coordinates isotype switching with plasma cell differentiation. Immunity 2006; 25: 225–236.

    Article  CAS  Google Scholar 

  30. Brustle A, Heink S, Huber M, Rosenplanter C, Stadelmann C, Yu P et al. The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4. Nat Immunol 2007; 8: 958–966.

    Article  Google Scholar 

  31. Barrett JC, Fry B, Maller J, Daly MJ . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21: 263–265.

    Article  CAS  Google Scholar 

  32. Qin ZS, Niu T, Liu JS . Partition-ligation-expectation-maximization algorithm for haplotype inference with single-nucleotide polymorphisms. Am J Hum Genet 2002; 71: 1242–1247.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was financially supported by the target-based funding by the Estonian Ministry of Education grant no. SF0180043s07, University of Tartu research grant no. PARFS 05901, Estonian Science Foundation grant nos. 6576, 5712 and 7549 and by the Centre of Molecular and Clinical Medicine grant VARMC-TIPP.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S Kõks.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kingo, K., Mössner, R., Rätsep, R. et al. Association analysis of IL20RA and IL20RB genes in psoriasis. Genes Immun 9, 445–451 (2008). https://doi.org/10.1038/gene.2008.36

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/gene.2008.36

Keywords

This article is cited by

Search

Quick links