Genetische Faktoren beim HELLP-Syndrom – eine kritische Übersicht

Zusammenfassung

Das HELLP-Syndrom ist eine schwere Form der Präeklampsie mit typischer laborchemischer Trias aus Hämolyse, pathologisch erhöhten Transaminasen und Thrombozytopenie < 100 000/µl und gehört auch heute noch zu den häufigsten Ursachen mütterlicher und kindlicher Morbidität und Mortalität und hat großen Anteil an der iatrogenen Frühgeburtlichkeit. Die Ätiologie und die zugrunde liegenden pathogenetischen Mechanismen sind noch nicht hinreichend geklärt. Eine genetische Komponente gilt mittlerweile als gesichert. Es gibt zahlreiche Hinweise, dass die immunologische Maladaptation, die plazentare Ischämie und der oxidative Stress einer genetischen Fehlsteuerung unterliegen. Die genetische Forschung bei Präeklampsie und HELLP-Syndrom umfasst genomweite Kopplungsanalysen, die Untersuchung von pathogenetisch vielversprechenden Kandidatengenen und Expressionsanalysen. Dabei wird deutlich, dass es das „Präeklampsie-“ oder „HELLP-Syndrom-Gen“ nicht gibt, sondern multifaktorielle, wahrscheinlich genetisch differente Determinanten an der Entstehung der Erkrankung beteiligt sind. Trotz intensiver Forschung gibt es bisher keine einheitlichen Ergebnisse, die die genetischen Mechanismen bei Präeklampsie/HELLP-Syndrom überzeugend erklären. Dabei sind unterschiedliche methodische Probleme bisheriger Studien unübersehbar. Die Zukunft dürfte in großen Multicenterstudien mit maternaler und fetaler Genotypisierung sowie genomweiten Assoziationsstudien liegen, die die gleichzeitige Analyse von mehreren tausend Polymorphismen ermöglichen.

Abstract

HELLP syndrome is a severe form of preeclampsia with a typical triad of hemolysis (H), elevated liver enzymes (EL) and low platelets (LP, thrombocytopenia < 100 000/µl) and remains a leading cause of maternal and perinatal mortality and morbidity, especially of preterm birth. The etiology and the underlying pathogenetic mechanisms are still unclear. Preeclampsia and HELLP syndrome have a clear genetic component, and immune maladaptation, placental ischemia and increased oxidative stress may all have genetic implications. Genetic research into preeclampsia and HELLP syndrome has focused on genome-wide linkage studies, the analysis of candidate genes and gene expression profiling. From the results obtained to date, it seems likely that not one single gene but rather a panel of different genetic determinants accounts for the susceptibility for HELLP syndrome and preeclampsia. Despite extensive research into preeclampsia and HELLP syndrome during the last decade, the exact genetic mechanisms are still unknown. This may at least in part be explained by the methodological problems of genetic association studies. Large multi-center studies including fetal and maternal genotyping and genome-wide association studies will be required to validate possible associations with preeclampsia and HELLP syndrome.

HELLP‐Syndrom - Kandidatengen - Polymorphismus

HELLP syndrome - candidate gene - polymorphism

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