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Neue Entwicklungen in der Psoriasisgenetik

New developments in the genetics of psoriasis

Zusammenfassung

Psoriasis vulgaris (PsV) ist eine chronische, entzündliche Hauterkrankung mit einer multifaktoriellen Vererbung. Nachdem der stärkste genetische Risikofaktor, das HLA-Cw0602-Allel (bzw. ein Allel in starkem Kopplungsungleichgewicht), insbesondere für die frühere Manifestationsform (<40. Lebensjahr), schon seit langem bekannt ist, konnten innerhalb der letzten beiden Jahre durch genomweite Assoziationsstudien sowie Untersuchungen von Kopienzahlveränderungen zahlreiche weitere Suszeptibilitätsfaktoren identifiziert werden. Zu den am besten replizierten Befunden zählen Varianten in 3 Genen des Interleukin-23-Rezeptor-Signalwegs. Außerdem konnten mehrere Gene des NFκB-Signalwegs (nukleärer Faktor κB) sowie ein Gen, dessen Produkt immunmodulatorisch in der TH2-Zell-vermittelten (TH-Zelle: T-Helfer-Zelle) Antwort wirkt, identifiziert werden. Neben dieser Bestätigung von PsV als einer immunologisch bedingten Erkrankung weisen mit PsV assoziierte Kopienzahlveränderungen auf eine zusätzliche zugrunde liegende Barrierestörung hin. Dies sind zum einen eine reduzierte Kopienzahl zweier epidermal exprimierter Gene des Clusters der Late-cornified-Envelope-Gene auf Chromosom 1q und zum anderen eine erhöhte Kopienzahl eines β-Defensin-Clusters auf Chromosom 8p.

Abstract

Psoriasis vulgaris (PsV) is an inflammatory disease of the skin characterized by complex inheritance. The strongest genetic risk factor, allele HLA-Cw0602 (or an allele in linkage disequilibrium with it), has been known for some time. This risk allele particularly predisposes to early manifestation (<40 years). Within the last 2 years, many further susceptibility alleles have been identified by genome-wide association studies and analyses of copy number changes. Besides HLA-C, variants in genes of the pathway of the interleukin-23 receptor are the best-known replicated risk factors for PsV. In addition, two genes of the NF-κB pathway (nuclear factor of kappa light polypeptide gene enhancer in B cells) as well as one gene coding for an immune modulator of the Th2-cell-mediated immune response were identified. These factors point to PsV as an immunological disease, but further associated copy number changes provide evidence for a contributing barrier dysfunction. These copy numbers are a deletion of two genes of the cluster containing late cornified envelope genes on chromosome 1q as well as an increased copy number of a ß-defensin cluster on chromosome 8p.

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Correspondence to U. Hüffmeier.

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Hüffmeier, U., Reis, A. Neue Entwicklungen in der Psoriasisgenetik. medgen 21, 498 (2009). https://doi.org/10.1007/s11825-009-0196-1

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Schlüsselwörter

  • IL-23R-Pathway
  • Kopienzahlpolymorphismus
  • β-Defensin-Cluster
  • Deletion zweier LCE-Gene
  • Genomweite Assoziationsstudien

Keywords

  • IL-23R pathway
  • Copy number polymorphism
  • β-defensin cluster
  • Deletion of two LCE genes
  • Genome-wide association studies