Wissenschaftliche Information:

Zusammenfassung: Die Beteiligung dieses Gens bei der Pathogenese von Bluthochdruck, hypertensiven Komplikationen und diabetischer Nephropathie wird diskutiert.

Gen: Das auf dem Chromosom 17 (17q23) lokalisierte Gen des Angiotensin converting enzyme besitzt eine Grösse von etwa 20kb erstreckt sich über 25 Exons.

Pathologie: Das Angiotensin-Converting-Enzyme (ACE) ist ein Enzym, welches extrazelulär Angiotensin I in Angiotensin II umwandelt Mit dem Angiotensin II entsteht ein sehr potenter Vasokonstriktor. Dem ACE kommt eine entscheidende Bedeutung im Renin-Angiotensin-System (RAS) zu, denn es vollzieht die letzte Aktivierungsstufe des Prohormons Angiotensinogen (AGT). Das aktivierte Angiotensinogen, das Angiotensin II, ist ein starker Vasokonstriktor und eine Stimulator der Aldosteronsynthese in den Nebennieren. In der Niere wird zudem die Mikrozirkulation und insbesondere die glomeruläre Filtrationsrate über den juxtaglomerulären Apparat gesteuert. Klinische Studien belegen gleichfalls die Bedeutung des RAS für die Entwicklung hypertensiver Folgeschäden. Molekulargenetische Untersuchungen am ACE-Gen konnten nun zeigen, dass es in zwei genetisch unterschiedlichen Varianten vorkommt. Diese beiden Allele unterscheiden sich um etwa 250 Basenpaare. Die längere Variante wird mit I (Insertion) und die kürzere mit D (Deletion) bezeichnet. Diese genetische Variante wird als Polymorphismus bezeichnet, da sie im Intron 16 des ACE-Gens lokalisiert ist und somit keinen Einfluß auf die Strktur des Enzyms selbst hat. Dieser Polymorphismus könnte dennoch für die Regulation des Gens eine wichtige Rolle spielen.

Klinik: Der Hypertonus ist eine weit verbreitete und durch viele genetische und Umweltfaktoren bedingte Erkrankung. Dem ACE-Polymorphismus könnte eine modifizierende Bedeutung bei der Ausprägung des Hypertonus und seiner Folgeerkrakungen zukommen.

Epidemiologie: Der Polymorphismus ist weltweit verbreitet. Für die Normalbevölkerung werden folgende Häufigkeiten angegeben. DD 34% DI 44% II 22%

Bewertung: Die größere Häufigkeit des D-Allels läßt vermuten, dass die Träger dieses Allels in der Vergangenheit in der Selektion bevorteilt waren. Allerdings läßt sich heute schwer entscheiden warum. Anhand der heute vorliegenden Studien verdichtet sich die Erkenntnis, dass Träger des D-Allels anfälliger für die modernen Zivilisationskrankheiten sind. Mit zunehmender Anzahl von D-Allelen steigt das Risiko für Herz-Kreislauf-Erkrankungen, für diabetische Spätschäden und für die Entwicklung renaler Komplikationen bei den verschiedensten Grunderkrankungen.

Methodik:

Literatur: 

Nagel M, BMC Nephrol. 2005 Jan 11;6(1):1
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