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Genetik der androgenetischen Alopezie

Genetics of androgenetic alopecia

Zusammenfassung

Die androgenetische Alopezie (AGA, erblich- bzw. hormonbedingter Haarausfall [MIM 109200; MIM 300710; MIM 612421]) ist die häufigste Form des Haarverlusts beim Menschen, wobei die Prävalenz stark altersabhängig ist. Im Alter von über 70 Jahren sind über 80% der europäischen Männer betroffen, bei Frauen liegt die AGA-Häufigkeit mit 30–40% deutlich niedriger. Die AGA führt, v. a. bei betroffenen Frauen, zu einer erheblichen psychologischen Belastung und entfaltet dabei Krankheitswert. Der Haarverlust geht auf einen veränderten Haarzyklus und eine Miniaturisierung des Haarfollikels zurück. Die Pathogenese ist androgenabhängig, und die genetische Anlage ist wesentliche Voraussetzung für den Phänotyp. In mehreren Studien konnten der Androgenrezeptor-/Ektodysplasin-A2-Rezeptor(EDA2R)-Locus auf dem X-Chromosom als stärkster beitragender Faktor und durch genomweite Assoziationsuntersuchungen ein weiterer Locus auf Chromosom 20p11 identifiziert werden. Das zum Assoziationssignal nächstgelegene in der Kopfhaut exprimierte Gen ist „paired box 1“ (PAX1). Zwischen PAX1 und dem Androgensignalweg gibt es keine offensichtliche Verbindung, jedoch sind die dem Assoziationssignal auf Chromosom 20p11 zugrunde liegenden pathophysiologischen Prozesse noch nicht geklärt. Bis heute ermöglichen die zur Verfügung stehenden medikamentösen Therapien der AGA bestenfalls ein Aufhalten des Haarverlusts. Mit der Identifizierung der AGA-assoziierten Gene und der Aufklärung ihrer Funktionen wird man die biologischen Ursachen der AGA schrittweise erschließen. Damit ist die Hoffnung auf die Entwicklung neuer Therapien verbunden.

Abstract

Androgenetic alopecia (AGA, male pattern baldness [MIM 109200; MIM 300710; MIM 612421]) is the commonest form of hair loss in humans, and its prevalence is highly age-dependent. Eighty per cent of European men above the age of 70 are affected by AGA, but only 30–40% of women. In many affected individuals, particularly women, AGA causes clinically significant psychological distress. Hair loss is attributable to an altered hair cycle and miniaturization of the hair follicles. The pathogenesis is androgen dependent, and genetic predisposition is an essential prerequisite of the phenotype. Several studies have identified the androgen receptor (AR)/ectodysplasin A2 receptor (EDA2R) locus on the X-chromosome as the strongest contributing factor. Genome wide association studies have identified a further locus on chromosome 20p11. The nearest scalp expressed gene to the association signal is paired box 1 (PAX1). Although there is no obvious connection between PAX1 and the androgen signalling pathway, the pathophysiological processes underlying the association signal for chromosome 20p11 have not yet been explained. At best, currently available therapies for AGA permit the arrest of hair loss. The identification of AGA associated genes and the elucidation of their function will gradually reveal the biological causes of AGA and offer hope for the development of new therapies.

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Brockschmidt, F., Hillmer, A., Kruse, R. et al. Genetik der androgenetischen Alopezie. medgen 21, 511 (2009). https://doi.org/10.1007/s11825-009-0197-0

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Schlüsselwörter

  • Androgenetische Alopezie
  • Erblich bedingter Haarausfall
  • Androgenrezeptor
  • Ektodysplasin-A2-Rezeptor
  • „Paired box 1“

Keywords

  • Androgenetic alopecia
  • Male pattern baldness
  • Androgen receptor
  • Ectodysplasin A2 receptor
  • Paired box 1