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Genetik der Psoriasis

Genetics of psoriasis

  • Schwerpunkt: Multifaktorielle Erkrankungen
  • Published:
medizinische genetik

Zusammenfassung

Psoriasis ist eine chronische, entzündliche Hauterkrankung mit einer multifaktoriellen Vererbung. Als wichtigster Risikofaktor gilt derzeit das HLA-CW0602-Allel [bzw. ein Faktor in starkem LD („linkage disequilibrium“)], das insbesondere für die frühere Manifestationsform (< 40. Lebensjahr) prädisponiert und u. a. einen Einfluss auf die Schwere des Verlaufs hat. Durch genomweite Kopplungsanalysen konnten bisher 11 weitere Suszeptibilitätsloci, jedoch nur wenige Kandidatengene identifiziert werden, alle mit vergleichsweise geringem relativem Risiko (Odds-Ratio, OR). Weitere Aspekte der komplexen Ätiopathogenese dieser Erkrankung konnten in immunologischen Ansätzen, aufgrund von Therapieerfolgen mit Antikörpern gegen immunrelevante Moleküle und bei kandidatengenorientierten Assoziationsstudien aufgeklärt werden. Die pathophysiologischen und genetischen Befunde konvergieren zunehmend und zeichnen die Psoriasis als Erkrankung eines fehlgesteuerten immunologischen Regulationsprozesses zwischen Keratinozyten und Zellen des angeborenen und erworbenen Immunsystems aus.

Abstract

Psoriasis is a complex inflammatory and cutaneous disorder with complex inheritance. Currently, the most important risk factor is HLA-CW0602 (and/or a factor in strong linkage disequilibrium with it). This risk allele particularly predisposes to early manifestation (<40 years) and affects the clinical course. To date, genome-wide linkage studies have provided 11 susceptibility loci, while only a few candidate genes have been identified, which bear comparably small odd ratios. Immunological approaches, therapeutic studies with antibodies against immunologic molecules, and candidate-gene-oriented association studies could delineate more aspects of the complex etiology of psoriasis. Increasingly, pathophysiologic and genetic findings converge, giving evidence that psoriasis can be characterized by misdirected immunologic regulation processes of keratinocytes and cells of the inborn and adaptive immune system.

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Literatur

  1. Asumalahti K, Ameen M, Suomela S et al. (2003) Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis. J Invest Dermatol 120: 627–632

    Article  PubMed  CAS  Google Scholar 

  2. Barton A, Bruce I, Silman A (2001) Genetic studies of psoriatic arthritis: dissecting joints and skin. J Rheumatol 28: 3–5

    PubMed  CAS  Google Scholar 

  3. Cargill M, Schrodi SJ, Chang M et al. (2007) A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 80: 273–290

    Article  PubMed  CAS  Google Scholar 

  4. Christophers E (2001) Psoriasis – epidemiology and clinical spectrum. Clin Exp Dermatol 26: 314–320

    Article  PubMed  CAS  Google Scholar 

  5. Cookson WO, Ubhi B, Lawrence R et al. (2001) Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci. Nat Genet 27: 372–373

    Article  PubMed  CAS  Google Scholar 

  6. Farber EM, Nall ML (1974) The natural history of psoriasis in 5,600 patients. Dermatologica 148: 1–18

    Article  PubMed  CAS  Google Scholar 

  7. Farber EM, Nall L (1991) Epidemiology: natural history and genetics. In: Roenigk HH, Maibach HI (eds) Psoriasis. Dekker, New York, pp 209–258.

  8. Giardina E, Capon F, De Rosa MC et al. (2004) Characterization of the loricrin (LOR) gene as a positional candidate for the PSORS4 psoriasis susceptibility locus. Ann Hum Genet 68: 639–645

    Article  PubMed  CAS  Google Scholar 

  9. Gudjonsson JE, Karason A, Antonsdottir A et al. (2002) HLA-Cw6-positive and HLA-Cw6-negative patients with psoriasis vulgaris have distinct clinical features. J Invest Dermatol 118: 362–365

    Article  PubMed  Google Scholar 

  10. Gudjonsson JE, Karason A, Antonsdottir A et al. (2003) Psoriasis patients who are homozygous for the HLA-Cw*0602 allele have a 2.5-fold increased risk of developing psoriasis compared with Cw6 heterozygotes. Br J Dermatol 148: 233–235

    Article  PubMed  CAS  Google Scholar 

  11. Gudjonsson JE, Karason A, Runarsdottir EH et al. (2006) Distinct clinical differences between HLA-Cw*0602 positive and negative psoriasis patients – an analysis of 1019 HLA-C- and HLA-B-typed patients. J Invest Dermatol 126: 740–745

    Article  PubMed  CAS  Google Scholar 

  12. Gudjonsson JE, Johnston A, Dyson M et al. (2007) Mouse models of psoriasis. J Invest Dermatol 127: 1292–1308

    Article  PubMed  CAS  Google Scholar 

  13. Helms C, Cao L, Krueger JG et al. (2003) A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis. Nat Genet 35: 349–356

    Article  PubMed  CAS  Google Scholar 

  14. Henseler T (1998) Genetics of psoriasis. Arch Dermatol Res 290: 463–476

    Article  PubMed  CAS  Google Scholar 

  15. Henseler T, Christophers E (1985) Psoriasis of early and late onset: characterization of two types of psoriasis vulgaris. J Am Acad Dermatol 13: 450–456

    Article  PubMed  CAS  Google Scholar 

  16. Hewett D, Samuelsson L, Polding J et al. (2002) Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map. Genomics 79: 305–314

    Article  PubMed  CAS  Google Scholar 

  17. Huffmeier U, Lascorz J, Traupe H et al. (2005) Systematic linkage disequilibrium analysis of SLC12A8 at PSORS5 confirms a role in susceptibility to psoriasis vulgaris. J Invest Dermatol 125: 906–912

    Article  PubMed  Google Scholar 

  18. Huffmeier U, Traupe H, Burkhardt H et al. (2005) Lack of evidence for genetic association to RUNX1 binding site at PSORS2 in different German psoriasis cohorts. J Invest Dermatol 124: 107–110

    Article  PubMed  Google Scholar 

  19. Huffmeier U, Traupe H, Oji V et al. (2007) Loss-of-function variants of the filaggrin gene are not major susceptibility factors for psoriasis vulgaris or psoriatic arthritis in German patients. J Invest Dermatol 127: 1367–1370

    Article  PubMed  CAS  Google Scholar 

  20. Iselius L, Williams WR (1984) The mode of inheritance of psoriasis: evidence for a major gene as well as a multifactorial component and its implication for genetic counselling. Hum Genet 68: 73–76

    Article  PubMed  CAS  Google Scholar 

  21. Karason A, Gudjonsson JE, Jonsson HH et al. (2005) Genetics of psoriasis in Iceland: evidence for linkage of subphenotypes to distinct loci. J Invest Dermatol 124: 1177–1185

    Article  PubMed  CAS  Google Scholar 

  22. Lowes MA, Bowcock AM, Krueger JG (2007) Pathogenesis and therapy of psoriasis. Nature 445: 866–873

    Article  PubMed  CAS  Google Scholar 

  23. Nair RP, Stuart PE, Nistor I et al. (2006) Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet 78: 827–851

    Article  PubMed  CAS  Google Scholar 

  24. Reich K, Hüffmeier U, König IR et al. (2007) TNF polymorphisms in psoriasis: association of psoriatic arthritis with the promoter polymorphism TNF-857 independent of the PSORS1 risk allele. Arthritis Rheum 56: 2056–2064

    Article  PubMed  CAS  Google Scholar 

  25. Sagoo GS, Tazi-Ahnini R, Barker JW et al. (2004) 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 122: 1401–1405

    Article  PubMed  CAS  Google Scholar 

  26. Swanbeck G, Inerot A, Martinsson T et al. (1994) A population genetic study of psoriasis. Br J Dermatol 131: 32–39

    Article  PubMed  CAS  Google Scholar 

  27. Swanbeck G, Inerot A, Martinsson T et al. (1997) Genetic counselling in psoriasis: empirical data on psoriasis among first-degree relatives of 3095 psoriatic probands. Br J Dermatol 137: 939–942

    Article  PubMed  CAS  Google Scholar 

  28. Taylor W, Gladman D, Helliwell P et al. (2006) Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 54: 2665–2673

    Article  PubMed  Google Scholar 

  29. Williams RC, McKenzie AW, Roger JH et al. (1976) HL-A antigens in patients with guttate psoriasis. Br J Dermatol 95: 163–167

    Article  PubMed  CAS  Google Scholar 

  30. Wrone-Smith T, Nickoloff BJ (1996) Dermal injection of immunocytes induces psoriasis. J Clin Invest 98: 1878–1887

    Article  PubMed  CAS  Google Scholar 

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Reis , A., Hüffmeier, U. Genetik der Psoriasis. medgen 19, 350–355 (2007). https://doi.org/10.1007/s11825-007-0034-2

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  • DOI: https://doi.org/10.1007/s11825-007-0034-2

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