Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Lipoprotein (a) Gen

Das LPA-Gen kodiert ein Plasminogen ähnliches Apolipoprotein, Lp(a), welches sich mit Welches sich mit Apolipoprotein B verbindet. Hohe Konzentrationen von Lp(a) sind mit einem hohen Risiko für Herz- und Kreislauferkrankungen verbunden. Genetisch sind Lp(a)-Spiegel von der Anzahl der Kringle IV-2-Repeats im Gen abhängig. Kurze Gene führen zu hohen Lp(a)-Spiegeln. Indirekt lässt sich die Anzahl der Kringle anhand zweier Polymorphismen (rs10455872 and rs3798220) feststellen.

Genstruktur

Das LPA-Gen und das Plasminogen-Gen (PLG) zeige eine große Sequenzhomologie. Beide Gene liegen auch unmittelbar hintereinander in einer Kopf-an-Kopf Position auf dem Chromosom 6 (6q26). Es wird angenommen, dass sich das LPA aus dem PLG durch Duplikation und anschließender Deletion und Copy-Number Variation entwickelt hat. Jedoch zeigen die Berechnungen beim 3'UTR (PLG-ferne Region) und 5'UTR (PLG-nahe Region) unterschiedliche Zeiten der Divergenz 40 bzw. 7 Millionen Jahre, so dass auch an ein zweizeitiges Ereignis gedacht werden könnte.

Während die Domain-Struktur des PLG-gens aud dem Signalpeptid, dem Schwanzteil, den Kringles 1-5 und eine Protease besteht, fehlt beim LPA-Gen das Schwanzteil und Kringles 1-3.

Die Protease domain des LPA ist sehr verschieden vom Plasminogen. Es wird überhaupt angezweifelt, dass diese Protease eine pathogenetische Bedeutung besitzt.

Interpretation

Die Minorallele der beiden SNPs (rs10455872 and rs3798220) kommen in der Normalbevölkerung mit einer Häufigkeit von 7% und 2% vor. 15% tragen wenigstens ein solches Minorallel. Unter den Patienten mit dem großen Lipoprotein (a) [Lp(a)] Phänotyp finden sich nur 2% Anlgeträger von einem der beiden Minorallele dieser SNPs. Bei den Trägern der kurzen Lp(a) Variante sind es dagegen 53%.

Diagnostik:

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

Krankheiten:

Arteriosklerose
APOB
APOE
HABP2
LDLR
LPA
MTHFR
PON1
SLC3A1
Lp(a) Hyperlipoproteinämie
LPA

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