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Genetik und personalisierte Medizin bei Asthma bronchiale

Genetics and personalized medicine in bronchial asthma

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Zusammenfassung

Asthma ist eine häufige und heterogene, chronisch entzündliche Erkrankung der Atemwege, bei der genetische und epigenetische Mechanismen in der Krankheitsentstehung eine Rolle spielen und zur besseren Klassifikation der unterschiedlichen Formen der Erkrankung genutzt werden könnten. Deutlich mehr Daten liegen zum Einfluss von Genetik und Epigenetik auf Asthma im Kindesalter als im Erwachsenenalter vor. Häufige Punktmutationen in Genen auf Chromosom 17 (ORMDL3, GSDMB) sind mit früh einsetzendem Asthma assoziiert, aber auch verschiedene Gene der klassischen Immunregulationswege wie IL4, -5, -13 und -33. Nicht nur Variationen der DNA (Desoxyribonukleinsäure) selbst, sondern auch durch Umweltfaktoren beeinflussbare epigenetische Veränderungen wie die Methylierungen von ZFPM1 und IL5RA tragen zur Asthmaentstehung bei. Genetik und Epigenetik beeinflussen auch die Wirkung bestimmter Therapien. Ein Polymorphismus in FCER2 steht mit dem schlechten Ansprechen auf inhalative Kortikosteroide in Zusammenhang, und die Hyposensibilisierung kann zur Demethylierung von FOXP3 führen, was wiederum regulatorische T‑Zellen beeinflusst. Genetik, Epigenetik, Pharmakogenetik und Pharmakoepigenetik können bei Diagnose und Therapiewahl zunehmend eine Rolle spielen und dazu beitragen, die verfügbaren Therapieoptionen zielgerichtet und personalisiert anzuwenden.

Abstract

Asthma is a frequent and heterogeneous, chronic inflammatory disease of the airways in which genetic and epigenetic mechanisms play a role in disease development and can be used for a better classification of the different forms of the disease. Significantly more data are available on the influence of genetics and epigenetics on childhood asthma than on adulthood asthma. Common point mutations (polymorphisms) in genes on chromosome 17 (ORMDL3, GSDMB) and on genes of the classical immune regulatory pathways, such as IL4, -5, -13 and -33 are associated with early onset asthma. Not only variations of the DNA itself but also epigenetic changes, influenced by environmental factors, such as methylation of ZFPM1 and IL5RA contribute to the development of asthma. The genetics and epigenetics also influence the effects of certain forms of treatment. A polymorphism in FCER2 is related to poor response to inhaled corticosteroids and desensitization leads to demethylation of FOXP3, which in turn affects regulatory T cells. Genetics, epigenetics, pharmacogenetics and pharmacoepigenetics can increasingly play a role in the diagnosis and choice of treatment and contribute to the targeted and personalized application of the available treatment options.

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Authors and Affiliations

  1. Klinik für pädiatrische Pneumologie und Allergologie, Kinder Uniklinik Ostbayern (KUNO) Regensburg, Barmherzige Brüder Klinik St. Hedwig, Steinmetzstr. 1–3, 93049, Regensburg, Deutschland

    Natascha S. Borchers, Elisangela Santos-Valente &  Michael Kabesch

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  1. Natascha S. Borchers
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  2. Elisangela Santos-Valente
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  3. Michael Kabesch
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Correspondence to Michael Kabesch.

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N.S. Borchers, E. Santos-Valente und M. Kabesch geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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C. Vogelmeier, Marburg

B. Schmeck, Marburg

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Borchers, N.S., Santos-Valente, E. & Kabesch, M. Genetik und personalisierte Medizin bei Asthma bronchiale. Pneumologe 18, 218–225 (2021). https://doi.org/10.1007/s10405-021-00384-3

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