ApoA5: Ein wichtiger Regulator der Triglyzeride oder nur ein weiteres Apoprotein?

Zusammenfassung

Apolipoprotein A5 (ApoA5) wurde 2001 zeitgleich durch Sequenzanalyse als Lipoprotein und als Regenerationsprotein der Leber entdeckt. Die wichtigste metabolische Funktion von ApoA5 ist die Senkung der Plasma-Triglyzeride (TG). Nach seiner hepatischer Produktion und Sekretion aktiviert ApoA5 die plasmatische, durch proteoglykangebundene Lipoproteinlipase (LPL) vermittelte TG-Hydrolyse von VLDL und Chylomikronen. Polymorphismen im ApoA5-Gen (z. B. - 1131T > C, S19W und G185C) sind vergleichsweise häufig und zeigen durchweg eine Assoziation mit erhöhten Plasma-TG-Spiegeln bei Patienten. Schwere strukturelle Proteinveränderungen (Q139X, Q148X, IVS3 + 3G > C, Q97X) können ähnlich wie Mutationen der LPL zur Chylomikronämie führen. Mehrere Studien fanden bei Vorliegen von ApoA5-Mutationen ein erhöhtes Risiko für Koronare Herzerkrankung. Interessanterweise legen die Ergebnisse einiger Publikationen nahe, dass bestimmte Polymorphismen im ApoA5-Gen das Ansprechen einer Fibrat-Therapie verbessern und vor Adipositas schützen könnten. Die Plasma-Konzentration von ApoA5 ist vergleichsweise gering (0,1-0,4 µg / ml); und es ist unklar, warum die ApoA5-Konzentration im Plasma in den meisten Studien positiv mit den TG-Spiegeln korreliert. ApoA5 ist also ein noch nicht lange bekannter wichtiger Determinator der Plasma-TG bei Patienten. Trotz einiger offener Fragen zu seiner molekularen Funktion sind weitere Daten zur diagnostischen und therapeutischen Relevanz von ApoA5 von sehr hohem klinischem Interesse.

Abstract

Apolipoprotein A5 (ApoA5) was discovered in 2001 simultaneously by comparative sequencing and as a liver regeneration protein. The most striking metabolic function of ApoA5 is the reduction of plasma triglyceride (TG). It is produced and secrated by the liver und activates the plasmatic, lipoprotein lipase (LPL) mediated hydrolysis of TG from VLDL and chylomicrons. ApoA5 gene polymorphisms (e. g., - 1131T > C, S19W and G185C) are quite common and they are consistently associated with plasma TG levels in patients. Severe structural mutations (Q139X, Q148X, IVS3 + 3G > C and Q97X) result into chylomicronemia, as do mutations in the LPL gene. Some studies show, that the presence of apoA5 mutations can increase the risk of coronary heart disease. At the other hand, there are publications suggesting that certain apoA5 polymorphisms can improve the sensibility to fibrates and protect from adiposity. The plasma concentration of apoA5 is low (0.1-0.4 µg / ml), and it is not clear, why its plasma concentration is positively correlated with TG levels. In conclusion, apo5 is a relatively new, important regulator of plasma TG levels in patients. Despite of some open questions, further information about its clinical diagnostic and therapeutic relevance is expected with great interest.

Schlüsselwörter

Lipide - Lipoprotein - Triglyzeride - Apoproteine - Arteriosklerose

Key words

lipids - lipoproteins - triglycerides - apoproteins - atherosclerosis

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