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Psoriasis: genetic associations and immune system changes

Abstract

Psoriasis is a common inflammatory skin disease characterized by infiltration of inflammatory cells into the epidermis and altered keratinocyte differentiation. Psoriasis is currently thought of as a T-cell mediated ‘Type-1’ autoimmune disease. Gene expression changes in psoriasis lesions have been well documented, and strongly support an important role for tumor necrosis factor and interferon gamma signal pathways in its pathogenesis. The strongest genetic determinant of psoriasis identified to date lies within the class I region of the multiple histocompatibility locus antigen cluster, although its low penetrance implicates a requirement for other genetic risk factors. Multiple genome-wide linkage and an increasing number of association studies have been carried out, leading to multiple linkage peaks, and the identification of potential low risk variants. A number of these variants lie within genes encoding components of the immune system. However, the functional relationships between predisposing genetic variation is unclear, and presumably involves genetic susceptibility factors affecting both immune cell activation and keratinocyte differentiation. The interaction of environmental trigger factors with genetic effects is also not understood, but provide further evidence for the complex basis of this disease.

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References

  1. Barisic-Drusko V, Rucevic I . Trigger factors in childhood psoriasis and vitiligo. Coll Antropol 2004; 28: 277–285.

    PubMed  Google Scholar 

  2. Quesada JR, Gutterman JU . Psoriasis and alpha-interferon. Lancet 1986; 1: 1466–1468.

    CAS  PubMed  Google Scholar 

  3. Gilliet M, Conrad C, Geiges M, Cozzio A, Thurlimann W, Burg G et al. Psoriasis triggered by toll-like receptor 7 agonist imiquimod in the presence of dermal plasmacytoid dendritic cell precursors. Arch Dermatol 2004; 140: 1490–1495.

    CAS  PubMed  Google Scholar 

  4. Zhou X, Krueger JG, Kao MC, Lee E, Du F, Menter A et al. Novel mechanisms of T-cell and dendritic cell activation revealed by profiling of psoriasis on the 63,100-element oligonucleotide array. Physiol Genomics 2003; 13: 69–78.

    CAS  PubMed  Google Scholar 

  5. Mansbridge JN, Knapp AM . Changes in keratinocyte maturation during wound healing. J Invest Dermatol 1987; 89: 253–263.

    CAS  PubMed  Google Scholar 

  6. Hertle MD, Kubler MD, Leigh IM, Watt FM . Aberrant integrin expression during epidermal wound healing and in psoriatic epidermis. J Clin Invest 1992; 89: 1892–1901.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Krane JF, Gottlieb AB, Carter DM, Krueger JG . The insulin-like growth factor I receptor is overexpressed in psoriatic epidermis, but is differentially regulated from the epidermal growth factor receptor. J Exp Med 1992; 175: 1081–1090.

    CAS  PubMed  Google Scholar 

  8. Ghadially R, Reed JT, Elias PM . Stratum corneum structure and function correlates with phenotype in psoriasis. J Invest Dermatol 1996; 107: 558–564.

    CAS  PubMed  Google Scholar 

  9. Allen M, Ishida-Yamamoto A, McGrath J, Davison S, Iizuka H, Simon M et al. Corneodesmosin expression in psoriasis vulgaris differs from normal skin and other inflammatory skin disorders. Lab Invest 2001; 81: 969–976.

    CAS  PubMed  Google Scholar 

  10. Abrams JR, Kelley SL, Hayes E, Kikuchi T, Brown MJ, Kang S et al. Blockade of T lymphocyte costimulation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells. J Exp Med 2000; 192: 681–694.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Ansel JC, Tiesman JP, Olerud JE, Krueger JG, Krane JF, Tara DC et al. Human keratinocytes are a major source of cutaneous platelet-derived growth factor. J Clin Invest 1993; 92: 671–678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Brown LF, Yeo KT, Berse B, Yeo TK, Senger DR, Dvorak HF et al. Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J Exp Med 1992; 176: 1375–1379.

    CAS  PubMed  Google Scholar 

  13. Viac J, Palacio S, Schmitt D, Claudy A . Expression of vascular endothelial growth factor in normal epidermis, epithelial tumors and cultured keratinocytes. Arch Dermatol Res 1997; 289: 158–163.

    CAS  PubMed  Google Scholar 

  14. Eckert RL, Broome AM, Ruse M, Robinson N, Ryan D, Lee K . S100 proteins in the epidermis. J Invest Dermatol 2004; 123: 23–33.

    CAS  PubMed  Google Scholar 

  15. Banno T, Adachi M, Mukkamala L, Blumenberg M . Unique keratinocyte-specific effects of interferon-gamma that protect skin from viruses, identified using transcriptional profiling. Antivir Ther 2003; 8: 541–554.

    CAS  PubMed  Google Scholar 

  16. Banno T, Gazel A, Blumenberg M . Effects of tumor necrosis factor-alpha (TNF alpha) in epidermal keratinocytes revealed using global transcriptional profiling. J Biol Chem 2004; 279: 32633–32642.

    CAS  PubMed  Google Scholar 

  17. Ferenczi K, Burack L, Pope M, Krueger JG, Austin LM . CD69, HLA-DR and the IL-2R identify persistently activated T cells in psoriasis vulgaris lesional skin: blood and skin comparisons by flow cytometry. J Autoimmun 2000; 14: 63–78.

    CAS  PubMed  Google Scholar 

  18. Austin LM, Ozawa M, Kikuchi T, Walters IB, Krueger JG . The majority of epidermal T cells in psoriasis vulgaris lesions can produce type 1 cytokines, interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients. J Invest Dermatol 1999; 113: 752–759.

    CAS  PubMed  Google Scholar 

  19. Vissers WH, Arndtz CH, Muys L, Van Erp PE, de Jong EM, van de Kerkhof PC . Memory effector (CD45RO+) and cytotoxic (CD8+) T cells appear early in the margin zone of spreading psoriatic lesions in contrast to cells expressing natural killer receptors, which appear late. Br J Dermatol 2004; 150: 852–859.

    CAS  PubMed  Google Scholar 

  20. Bos JD, Hagenaars C, Das PK, Krieg SR, Voorn WJ, Kapsenberg ML . Predominance of ‘memory’ T cells (CD4+, CDw29+) over ‘naive’ T cells (CD4+, CD45R+) in both normal and diseased human skin. Arch Dermatol Res 1989; 281: 24–30.

    CAS  PubMed  Google Scholar 

  21. Rottman JB, Smith TL, Ganley KG, Kikuchi T, Krueger JG . Potential role of the chemokine receptors CXCR3, CCR4, and the integrin alphaEbeta7 in the pathogenesis of psoriasis vulgaris. Lab Invest 2001; 81: 335–347.

    CAS  PubMed  Google Scholar 

  22. Austin LM, Coven TR, Bhardwaj N, Steinman R, Krueger JG . Intraepidermal lymphocytes in psoriatic lesions are activated GMP-17(TIA-1)+CD8+CD3+ CTLs as determined by phenotypic analysis. J Cutan Pathol 1998; 25: 79–88.

    CAS  PubMed  Google Scholar 

  23. Yawalkar N, Schmid S, Braathen LR, Pichler WJ . Perforin and granzyme B may contribute to skin inflammation in atopic dermatitis and psoriasis. Br J Dermatol 2001; 144: 1133–1139.

    CAS  PubMed  Google Scholar 

  24. Chamian F, Lowes MA, Lin SL, Lee E, Kikuchi T, Gilleaudeau P et al. Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris. Proc Natl Acad Sci USA 2005; 102: 2075–2080.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Lowes MA, Chamian F, Abello MV, Fuentes-Duculan J, Lin SL, Nussbaum R et al. Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). Proc Natl Acad Sci USA 2005; 102: 19057–19062.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 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.

    CAS  PubMed  Google Scholar 

  27. Nestle FO, Turka LA, Nickoloff BJ . Characterization of dermal dendritic cells in psoriasis. Autostimulation of T lymphocytes and induction of Th1 type cytokines. J Clin Invest 1994; 94: 202–209.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Lee E, Trepicchio WL, Oestreicher JL, Pittman D, Wang F, Chamian F et al. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med 2004; 199: 125–130.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Wollenberg A, Wagner M, Gunther S, Towarowski A, Tuma E, Moderer M et al. Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases. J Invest Dermatol 2002; 119: 1096–1102.

    CAS  PubMed  Google Scholar 

  30. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL . Interleukin-23 promotes a distinct CD4T cell activation state characterized by the production of interleukin-17. J Biol Chem 2003; 278: 1910–1914.

    CAS  PubMed  Google Scholar 

  31. Teunissen MB, Koomen CW, de Waal Malefyt R, Wierenga EA, Bos JD . Interleukin-17 and interferon-gamma synergize in the enhancement of proinflammatory cytokine production by human keratinocytes. J Invest Dermatol 1998; 111: 645–649.

    CAS  PubMed  Google Scholar 

  32. Bowcock AM, Krueger JG . Getting under the skin: the immunogenetics of psoriasis. Nat Rev Immunol 2005; 5: 699–711.

    CAS  PubMed  Google Scholar 

  33. Lew W, Bowcock AM, Krueger JG . Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and ‘Type 1’ inflammatory gene expression. Trends Immunol 2004; 25: 295–305.

    CAS  PubMed  Google Scholar 

  34. Lowes MA, Lew W, Krueger JG . Current concepts in the immunopathogenesis of psoriasis. Dermatol Clin 2004; 22: 349–369, vii.

    CAS  PubMed  Google Scholar 

  35. Kauffman CL, Aria N, Toichi E, McCormick TS, Cooper KD, Gottlieb AB et al. A phase I study evaluating the safety, pharmacokinetics, and clinical response of a human IL-12 p40 antibody in subjects with plaque psoriasis. J Invest Dermatol 2004; 123: 1037–1044.

    CAS  PubMed  Google Scholar 

  36. Boehncke WH, Prinz J, Gottlieb AB . Biologic therapies for psoriasis. A systematic review. J Rheumatol 2006; 33: 1447–1451.

    PubMed  Google Scholar 

  37. Ragaz A, Ackerman AB . Evolution, maturation, and regression of lesions of psoriasis. New observations and correlation of clinical and histologic findings. Am J Dermatopathol 1979; 1: 199–214.

    CAS  PubMed  Google Scholar 

  38. Kurth I, Willimann K, Schaerli P, Hunziker T, Clark-Lewis I, Moser B . Monocyte selectivity and tissue localization suggests a role for breast and kidney-expressed chemokine (BRAK) in macrophage development. J Exp Med 2001; 194: 855–861.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Elder JT, Nair RP, Guo SW, Henseler T, Christophers E, Voorhees JJ . The genetics of psoriasis. Arch Dermatol 1994; 130: 216–224.

    CAS  PubMed  Google Scholar 

  40. Bowcock AM . Psoriasis genetics: the way forward. J Invest Dermatol 2004; 122: xv–xvii.

    CAS  PubMed  Google Scholar 

  41. Tiilikainen A, Lassus A, Karvonen J, Vartiainen P, Julin M . Psoriasis and HLA-Cw6. Br J Dermatol 1980; 102: 179–184.

    CAS  PubMed  Google Scholar 

  42. Asumalahti K, Veal C, Laitinen T, Suomela S, Allen M, Elomaa O et al. Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus. Hum Mol Genet 2002; 11: 589–597.

    CAS  PubMed  Google Scholar 

  43. Allen MH, Veal C, Faassen A, Powis SH, Vaughan RW, Trembath RC et al. A non-HLA gene within the MHC in psoriasis. Lancet 1999; 353: 1589–1590.

    CAS  PubMed  Google Scholar 

  44. Guerrin M, Vincent C, Simon M, Tazi Ahnini R, Fort M, Serre G . Identification of six novel polymorphisms in the human corneodesmosin gene. Tissue Antigens 2001; 57: 32–38.

    CAS  PubMed  Google Scholar 

  45. Tazi Ahnini R, Camp NJ, Cork MJ, Mee JB, Keohane SG, Duff GW et al. Novel genetic association between the corneodesmosin (MHC S) gene and susceptibility to psoriasis. Hum Mol Genet 1999; 8: 1135–1140.

    CAS  PubMed  Google Scholar 

  46. Simon M, Jonca N, Guerrin M, Haftek M, Bernard D, Caubet C et al. Refined characterization of corneodesmosin proteolysis during terminal differentiation of human epidermis and its relationship to desquamation. J Biol Chem 2001; 276: 20292–20299.

    CAS  PubMed  Google Scholar 

  47. Jonca N, Guerrin M, Hadjiolova K, Caubet C, Gallinaro H, Simon M et al. Corneodesmosin, a component of epidermal corneocyte desmosomes, displays homophilic adhesive properties. J Biol Chem 2002; 277: 5024–5029.

    CAS  PubMed  Google Scholar 

  48. Gallinaro H, Jonca N, Langbein L, Vincent C, Simon M, Serre G et al. A 4.2 kb upstream region of the human corneodesmosin gene directs site-specific expression in hair follicles and hyperkeratotic epidermis of transgenic mice. J Invest Dermatol 2004; 122: 730–738.

    CAS  PubMed  Google Scholar 

  49. Veal CD, Capon F, Allen MH, Heath EK, Evans JC, Jones A et al. Family-based analysis using a dense single-nucleotide polymorphism-based map defines genetic variation at PSORS1, the major psoriasis-susceptibility locus. Am J Hum Genet 2002; 71: 554–564.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Helms C, Saccone NL, Cao L, Daw JA, Cao K, Hsu TM et al. Localization of PSORS1 to a haplotype block harboring HLA-C and distinct from corneodesmosin and HCR. Hum Genet 2005; 118: 466–476.

    CAS  PubMed  Google Scholar 

  51. Nair RP, Stuart PE, Nistor I, Hiremagalore R, Chia NV, Jenisch S et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet 2006; 78: 827–851.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Altshuler D, Brooks LD, Chakravarti A, Collins FS, Daly MJ, Donnelly P . A haplotype map of the human genome. Nature 2005; 437: 1299–1320.

    Google Scholar 

  53. Asumalahti K, Laitinen T, Lahermo P, Suomela S, Itkonen-Vatjus R, Jansen C et al. Psoriasis susceptibility locus on 18p revealed by genome scan in Finnish families not associated with PSORS1. J Invest Dermatol 2003; 121: 735–740.

    CAS  PubMed  Google Scholar 

  54. Tomfohrde J, Silverman A, Barnes R, Fernandez-Vina MA, Young M, Lory D et al. Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q. Science 1994; 264: 1141–1145.

    CAS  PubMed  Google Scholar 

  55. Tzschach A, Hoffmann K, Hoeltzenbein M, Bache I, Tommerup N, Bommer C et al. Molecular characterization of a balanced chromosome translocation in psoriasis vulgaris. Clin Genet 2006; 69: 189–193.

    CAS  PubMed  Google Scholar 

  56. Hwu WL, Yang CF, Fann CS, Chen CL, Tsai TF, Chien YH et al. Mapping of psoriasis to 17q terminus. J Med Genet 2005; 42: 152–158.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Birnbaum RY, Zvulunov A, Hallel-Halevy D, Cagnano E, Finer G, Ofir R et al. Seborrhea-like dermatitis with psoriasiform elements caused by a mutation in ZNF750, encoding a putative C2H2 zinc finger protein. Nat Genet 2006; 38: 749–751.

    CAS  PubMed  Google Scholar 

  58. Helms C, Cao L, Krueger JG, Wijsman EM, Chamian F, Gordon D et al. A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis (see comment). Nat Genet 2003; 35: 349–356.

    CAS  PubMed  Google Scholar 

  59. Prokunina L, Castillejo-Lopez C, Oberg F, Gunnarsson I, Berg L, Magnusson V et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet 2002; 32: 666–669.

    CAS  PubMed  Google Scholar 

  60. Tokuhiro S, Yamada R, Chang X, Suzuki A, Kochi Y, Sawada T et al. An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis (see comment). Nat Genet 2003; 35: 341–348.

    CAS  PubMed  Google Scholar 

  61. Coffman JA . Runx transcription factors and the developmental balance between cell proliferation and differentiation. Cell Biol Int 2003; 27: 315–324.

    CAS  PubMed  Google Scholar 

  62. Osato M, Yanagida M, Shigesada K, Ito Y . Point mutations of the RUNx1/AML1 gene in sporadic and familial myeloid leukemias. Int J Hematol 2001; 74: 245–251.

    CAS  PubMed  Google Scholar 

  63. Fainaru O, Woolf E, Lotem J, Yarmus M, Brenner O, Goldenberg D et al. Runx3 regulates mouse TGF-beta-mediated dendritic cell function and its absence results in airway inflammation. EMBO J 2004; 23: 969–979.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Brenner O, Levanon D, Negreanu V, Golubkov O, Fainaru O, Woolf E et al. Loss of Runx3 function in leukocytes is associated with spontaneously developed colitis and gastric mucosal hyperplasia. Proc Natl Acad Sci USA 2004; 101: 16016–16021.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Grueter B, Petter M, Egawa T, Laule-Kilian K, Aldrian CJ, Wuerch A et al. Runx3 regulates integrin alpha E/CD103 and CD4 expression during development of CD4−/CD8+ T cells. J Immunol 2005; 175: 1694–1705.

    CAS  PubMed  Google Scholar 

  66. Capon F, Helms C, Veal CD, Tillman D, Burden AD, Barker JN et al. Genetic analysis of PSORS2 markers in a UK dataset supports the association between RAPTOR SNPs and familial psoriasis. J Med Genet 2004; 41: 459–460.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Hewett D, Samuelsson L, Polding J, Enlund F, Smart D, Cantone K et al. Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map. Genomics 2002; 79: 305–314.

    CAS  PubMed  Google Scholar 

  68. Hebert SC, Mount DB, Gamba G . Molecular physiology of cation-coupled Cl-cotransport: the SLC12 family. Pflugers Arch 2004; 447: 580–593.

    CAS  PubMed  Google Scholar 

  69. Huffmeier U, Lascorz J, Traupe H, Bohm B, Schurmeier-Horst F, Stander M et al. Systematic linkage disequilibrium analysis of SLC12A8 at PSORS5 confirms a role in susceptibility to psoriasis vulgaris. J Invest Dermatol 2005; 125: 906–912.

    PubMed  Google Scholar 

  70. Capon F, Novelli G, Semprini S, Clementi M, Nudo M, Vultaggio P et al. Searching for psoriasis susceptibility genes in Italy: genome scan and evidence for a new locus on chromosome 1. J Invest Dermatol 1999; 112: 32–35.

    CAS  PubMed  Google Scholar 

  71. Bhalerao J, Bowcock AM . The genetics of psoriasis: a complex disorder of the skin and immune system. Hum Mol Genet 1998; 7: 1537–1545.

    CAS  PubMed  Google Scholar 

  72. Capon F, Semprini S, Dallapiccola B, Novelli G . Evidence for interaction between psoriasis-susceptibility loci on chromosomes 6p21 and 1q21. Am J Hum Genet 1999; 65: 1798–1800.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Cookson WO, Ubhi B, Lawrence R, Abecasis GR, Walley AJ, Cox HE et al. Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci. Nat Genet 2001; 27: 372–373.

    CAS  PubMed  Google Scholar 

  74. Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 2006; 38: 441–446.

    CAS  PubMed  Google Scholar 

  75. Morar N, Bowcock AM, Harper JI, Cookson WO, Moffatt MF . Investigation of the chromosome 17q25 PSORS2 locus in atopic dermatitis. J Invest Dermatol 2006; 126: 603–606.

    CAS  PubMed  Google Scholar 

  76. Sagoo GS, Tazi-Ahnini R, Barker JW, Elder JT, Nair RP, Samuelsson L et al. Meta-analysis of genome-wide studies of psoriasis susceptibility reveals linkage to chromosomes 6p21 and 4q28–q31 in Caucasian and Chinese Hans population. J Invest Dermatol 2004; 122: 1401–1405.

    CAS  PubMed  Google Scholar 

  77. Foerster J, Nolte I, Schweiger S, Ehlert C, Bruinenberg M, Spaar K et al. Evaluation of the IRF-2 gene as a candidate for PSORS3. J Invest Dermatol 2004; 122: 61–64.

    CAS  PubMed  Google Scholar 

  78. Yan KL, Zhang XJ, Wang ZM, Yang S, Zhang GL, Wang J et al. A novel MGST2 non-synonymous mutation in a Chinese pedigree with psoriasis vulgaris. J Invest Dermatol 2006; 126: 1003–1005.

    CAS  PubMed  Google Scholar 

  79. Yang S, Yan KL, Zhang XJ, Xiao FL, Fan X, Gao M et al. Systematic evaluation of association between the microsomal glutathione S-transferase 2 common variation and psoriasis vulgaris in Chinese population. Arch Dermatol Res 2006; 298: 107–112.

    PubMed  Google Scholar 

  80. Becker KG, Simon RM, Bailey-Wilson JE, Freidlin B, Biddison WE, McFarland HF et al. Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases. Proc Natl Acad Sci USA 1998; 95: 9979–9984.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Begovich AB, Carlton VE, Honigberg LA, Schrodi SJ, Chokkalingam AP, Alexander HC et al. A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 2004; 75: 330–337.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M et al. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 2004; 36: 337–338.

    CAS  PubMed  Google Scholar 

  83. Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, Carlton VE et al. Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet 2004; 75: 504–507.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Huffmeier U, Steffens M, Burkhardt H, Lascorz J, Schurmeier-Horst F, Stander M et al. Evidence for susceptibility determinant(s) to psoriasis vulgaris in or near PTPN22 in German patients. J Med Genet 2006; 43: 517–522.

    CAS  PubMed  Google Scholar 

  85. Guo D, Li M, Zhang Y, Yang P, Eckenrode S, Hopkins D et al. A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes. Nat Genet 2004; 36: 837–841.

    CAS  PubMed  Google Scholar 

  86. Lizzul PF, Aphale A, Malaviya R, Sun Y, Masud S, Dombrovskiy V et al. Differential expression of phosphorylated NF-kappaB/RelA in normal and psoriatic epidermis and downregulation of NF-kappaB in response to treatment with etanercept. J Invest Dermatol 2005; 124: 1275–1283.

    CAS  PubMed  Google Scholar 

  87. Mossner R, Kingo K, Kleensang A, Kruger U, Konig IR, Silm H et al. Association of TNF-238 and -308 promoter polymorphisms with psoriasis vulgaris and psoriatic arthritis but not with pustulosis palmoplantaris. J Invest Dermatol 2005; 124: 282–284.

    PubMed  Google Scholar 

  88. Reich K, Westphal G, Schulz T, Muller M, Zipprich S, Fuchs T et al. Combined analysis of polymorphisms of the tumor necrosis factor-alpha and interleukin-10 promoter regions and polymorphic xenobiotic metabolizing enzymes in psoriasis. J Invest Dermatol 1999; 113: 214–220.

    CAS  PubMed  Google Scholar 

  89. Litjens NH, van der Plas MJ, Ravensbergen B, Numan-Ruberg SC, van Assen Y, Thio HB et al. Psoriasis is not associated with IL-12p70/IL-12p40 production and IL12B promoter polymorphism. J Invest Dermatol 2004; 122: 923–926.

    CAS  PubMed  Google Scholar 

  90. Tsunemi Y, Saeki H, Nakamura K, Sekiya T, Hirai K, Fujita H et al. Interleukin-12 p40 gene (IL12B) 3′-untranslated region polymorphism is associated with susceptibility to atopic dermatitis and psoriasis vulgaris. J Dermatol Sci 2002; 30: 161–166.

    CAS  PubMed  Google Scholar 

  91. Begovich AB, Schrodi SJ, Leppert M, Krueger G, Cargill M . A genome-wide association study of putative functional SNPs leads to the identification of two psoriasis loci – IL12B and IL23R – in 3 independent white North American sample sets. Am J Hum Genet 2006; Society meeting abstracts: A163.

  92. Trinchieri G . Cytokines and cytokine receptors. Immunol Rev 2004; 202: 5–7.

    PubMed  Google Scholar 

  93. Beissert S, Ruhlemann D, Mohammad T, Grabbe S, El-Ghorr A, Norval M et al. IL-12 prevents the inhibitory effects of cis-urocanic acid on tumor antigen presentation by Langerhans cells: implications for photocarcinogenesis. J Immunol 2001; 167: 6232–6238.

    CAS  PubMed  Google Scholar 

  94. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 2005; 6: 1123–1132.

    CAS  PubMed  Google Scholar 

  95. Mangan PR, Harrington LE, O'Quinn DB, Helms WS, Bullard DC, Elson CO et al. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 2006; 441: 231–234.

    CAS  PubMed  Google Scholar 

  96. Koks S, Kingo K, Vabrit K, Ratsep 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.

    CAS  PubMed  Google Scholar 

  97. Asadullah K, Eskdale J, Wiese A, Gallagher G, Friedrich M, Sterry W . Interleukin-10 promoter polymorphism in psoriasis. J Invest Dermatol 2001; 116: 975–978.

    CAS  PubMed  Google Scholar 

  98. Hensen P, Asadullah K, Windemuth C, Ruschendorf F, Huffmeier U, Stander M et al. Interleukin-10 promoter polymorphism IL10.G and familial early onset psoriasis. Br J Dermatol 2003; 149: 381–385.

    CAS  PubMed  Google Scholar 

  99. Kingo K, Koks S, Silm H, Vasar E . IL-10 promoter polymorphisms influence disease severity and course in psoriasis. Genes Immun 2003; 4: 455–457.

    CAS  PubMed  Google Scholar 

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Liu, Y., Krueger, J. & Bowcock, A. Psoriasis: genetic associations and immune system changes. Genes Immun 8, 1–12 (2007). https://doi.org/10.1038/sj.gene.6364351

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