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Genetik des Typ-2-Diabetes

  • Robert Wagner
  • Harald StaigerEmail author
CME
  • 11 Downloads

Zusammenfassung

Typ-2-Diabetes ist eine multifaktorielle Erkrankung mit ausgeprägter polygenetischer Komponente. Mit Hilfe familienbasierter Kopplungsanalysen, kandidatengenbasierter Genotyp-Phänotyp-Assoziationsanalysen sowie, am erfolgreichsten, hypothesenfreier genomweiter Assoziationsanalysen wurden bisher 403 unabhängige, überwiegend häufig vorkommende Genvarianten in 243 Loci identifiziert, die das Typ-2-Diabetes-Risiko signifikant erhöhen. Die Genvariante mit dem diesbezüglich robustesten Effekt befindet sich im TCF7L2-Gen (TCF7L2: „transcription factor 7‑like 2“) und vermindert die Inkretinsensitivität der pankreatischen β‑Zellen und das therapeutische Ansprechen auf Inkretinachsenmedikamente. Derartige pathomechanistische Einblicke gibt es heute nur zu sehr wenigen Typ-2-Diabetes-Genen. Diesbezügliche Untersuchungen werden durch Gen-Gen‑, Gen-Lebensstil- und Gen-Umwelt-Interaktionen erschwert. Auch darum ist die Bedeutung der Risikoallele für die Typ-2-Diabetes-Prädiktion noch sehr begrenzt.

Schlüsselwörter

Nichtinsulinabhängiger Diabetes mellitus Störungen des Glukosestoffwechsels Genloci Vererbungsmöglichkeiten Polymorphismus, genetischer 

Genetic background of type 2 diabetes

Abstract

Type 2 diabetes mellitus is a multifactorial disease with an obvious polygenetic component. Using family-based linkage analysis, candidate gene-based genotype–phenotype association analysis, and the by far most successful method of hypothesis-free genome-wide association analysis, a total of 403 independent, mostly common gene variants in 243 gene loci significantly associated with type 2 diabetes risk have been hitherto identified. The gene variant with the most robust effect on type 2 diabetes risk is located in the TCF7L2 (transcription factor 7‑like 2) gene locus and reduces incretin sensitivity of pancreatic β‑cells and limits the therapeutic response to drugs that make use of the incretin axis. Such pathomechanistic insights are currently only available for very few of the type 2 diabetes genes. Pathomechanistic investigations are hampered by gene–gene, gene–lifestyle, and gene–environment interactions. This is one of the main reasons why the impact of the risk alleles on type 2 diabetes prediction is still very limited.

Keywords

Diabetes mellitus, non-insulin dependent Glucose metabolism disorders Genetic loci Inheritance patterns Polymorphism, genetic 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

R. Wagner und H. Staiger 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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Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.Institut für Diabetesforschung und Metabolische Erkrankungen des Helmholtz Zentrums München an der Universität TübingenHelmholtz Zentrum MünchenTübingenDeutschland

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