Mutationsanalyse der Gene PlGF und FLT1 bei Patientinnen mit IUGR und ARED-Flow im Doppler der A. umbilicalis
The development of the fetoplacental system, i.e. capillary sprouting as well as the switch from branching to non-branching angiogenesis, in human pregnancy is essential for the birth of a healthy infant at term. This angiogenic process is controlled by growth factors such as bFGF, VEGF and PlGF. The interaction of PlGF with FLT1 seems to induce non-branching angiogenesis and this type of angiogenesis predominates in pregnancies with intrauterine growth retardation (IUGR) and ARED (absent or reversed enddiastolic)-flow (postplacental hypoxia). In pregnancies with IUGR and PED (preserved enddiastolic)-flow in the presence of a bilateral abnormal uterine artery Doppler waveform (uteroplacental hypoxia), histology of the placenta shows a netlike arrangement of capillaries, forming multiply branched terminal villi.To study a possible role of mutations in the PlGF and the FLT1 genes in the pathogenesis of placental dysfunction, we analysed the PIGF and FLT1 genes in an IUGR/ARED-flow group (18 mothers and 18 fetuses) and an IUGR/PED-flow group (14 mothers and 14 fetuses). DNA was extracted from venous blood samples (mothers) and umibilical cord blood samples (fetuses). The coding sequences of PlGF (7 exons) and FLT1 (30 exons) and their intron/exon boundaries were screened by single strand conformation polymorphism analysis (SSCP), restriction assays and direct sequencing.Apart from established SNPs, we identified one new polymophism in exon 1 of the non-coding sequence of PlGF and two novel variants in exons 1 and 6 of FLT1 (table 1). The variations were detected in similar frequencies in the two groups. We could not identify a pathogenic mutation neither in the PlGF gene nor in the FLT1 gene, providing no evidence for a relevant role of both genes in the aetiology of IUGR/ARED or IUGR/PED. Propably an analysis of further pregnancies with IUGR and ARED- or PED- flow could help to identify such pathogenic mutations.
info:eu-repo/classification/ddc/610, Medizin, Präeklampsie, HELLP-Syndrom, Pränatale Dystrophie, PlGF, FLT1, ARED, PED, IUGR, branching angiogenesis, non-branching angiogenesis
Networked Digital Library of Theses and Dissertations
Publikationsserver der RWTH Aachen University