Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Angiotensin Converting Enzym

Die Beteiligung des ACE Gens bei der Pathogenese von Bluthochdruck, hypertensiven Komplikationen und diabetischer Nephropathie wird diskutiert.

Epidemiologie

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

Genstruktur

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

Phänotyp

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.

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.

Interpretation

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.

Diagnostik:

Clinic Untersuchungsmethoden Familienuntersuchung
Bearbeitungszeit 5
Probentyp genomic DNA
Clinic Untersuchungsmethoden Direkte Sequenzierung der proteinkodierenden Bereiche eines Gens
Bearbeitungszeit 20
Probentyp genomic DNA
Clinic Untersuchungsmethoden Direkte Sequenzierung ausgewählter Gen-Abschnitte
Bearbeitungszeit 20
Probentyp genomic DNA
Clinic Untersuchungsmethoden Hochdurchsatz-Sequenzierung
Bearbeitungszeit 25
Probentyp genomic DNA

Krankheiten:

Diabetische Nephropathie
ACE
AGT
AKR1B1
Erblicher Bluthochdruck
ACE
ACE2
AGT
Benigne Hyperproreninämie
REN
Monogener Hypertonus
Apparenter Mineralocortocoid Exzess
HSD11B2
Glycocorticoid getriggerter Hypertonus
NR3C1
Hyperaldosteronismus
Conn-Syndrom
ATP1A1
ATP2B3
CACNA1D
CACNA1H
CTNNB1
KCNJ5
Glycocorticoid getriggerter Hypertonus
NR3C1
Hyperaldosteronismus Typ 1
CYP11B1
CYP11B2
Hyperaldosteronismus Typ 2
Hyperaldosteronismus Typ 3
KCNJ5
Hyperaldosteronismus Typ 4
CACNA1D
CACNA1H
Hypertonie-Brachydaktylie-Syndrom
PDE3A
Liddle-Syndrom
NEDD4
NEDD4L
NR3C2
OXSR1
SCNN1B
SCNN1G
STK39
Pseudohypoaldosteronismus
Pseudohypoaldosteronismus Typ 1
NR3C2
SCNN1A
SCNN1B
SCNN1G
Pseudohypoaldosteronismus Type 2
CUL3
KLHL3
WNK1
WNK4
Salzsensitiver essentieller Hypertonus
CYP3A5
VEGFC
Renotubuläre Dysgenesie
ACE
AGT
AGTR1
REN

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