Preeclampsia triggered by an overdose of gene activity

Preeclampsia is the most dangerous form of hypertension during a pregnancy and can be fatal for both mother and child. Though it is known to originate in the placenta, the root causes remain largely a mystery. An international research team led by the Max Delbrück Center for Molecular Medicine (MDC) has recently published new findings which reveal that preeclampsia is not in fact a single disease caused solely by genetic factors. Their tests on placenta samples have shown that epigenetically regulated genes play an important role. The Berlin research team also developed an in vitro model of the disorder which demonstrates the dysregulation of an important transcription factor.
The research team compared placental tissue samples and the genetic makeup of patients with preeclampsia with those of healthy women. The entirety of their genetic material was analysed for genes that are differentially expressed in the preeclamptic versus healthy placentas and checked for disrupted genomic imprinting, which refers to certain genes that are “switched off” on either the paternal or maternal chromosome. This led them to identify the so-called DLX5 gene as a significant transcription factor involved in regulating the activity of other genes in preeclampsia. This gene is usually turned off – or epigenetically “imprinted” – on the paternal chromosome, controlling the proper dosage of gene expression. Due to loss of the regulation by imprinting, DLX5 was strongly upregulated in ca. 70 percent of the samples studied from preeclampsia patients, meaning the gene was switched on in these cases. This study is the first to demonstrate that a change in epigenetic gene regulation by imprinting can contribute to preeclampsia. The scientists also found three separate types of preeclampsia, supporting the view that preeclampsia is a complex disease.

Max Delbrück Center for Molecular Medicine
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