maternal polymorphism plays a role in PE phenotype

[caryn]

Maternal endothelin-1 is elevated and correlates with the severity of blood pressure elevation in preeclampsia. The endothelin-1 is likely released from the maternal endothelium. Presence of T allele at 5665 position in maternal EDN1 gene is associated with higher endothelin-1 levels. Placental endothelin-1 synthesis is reduced in preeclampsia. The combination of elevated maternal and reduced placental endothelin-1 may be an adaptive response to reduced uteroplacental flow in preeclampsia.

http://www.ncbi.nlm.nih.gov/pubmed/19730395

Read in conjunction with the [url="http://www.preeclampsia.org/forum/viewtopic.php?t=36499"]study about 17-p[/url] that I just posted, this illustrates pretty nicely what we're up against here. First: it's genetic. Second: it's adaptive, and blocking it might not be the best idea. When there's not enough bloodflow into the placenta, doing things that lower the maternal blood pressure has the potential to compromise the placental perfusion, and thus the baby. This is why we have [url="http://www.smfm.org"]maternal-fetal medicine specialists[/url] to balance the competing demands of mother and baby -- delivery and blood pressure control are always appropriate therapy for the mother, but not for the baby -- and why this is such a difficult disease to treat or cure.

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[jules2]

My daughter died in utero very unexpectedly (I had an us showing normal umbilical artery blood flow only about 20 hours before death), and I have often wondered if lowering my blood pressure was a factor in this. Not that I am blaming the docs, they could not let me wander around with a BP of 190/100 untreated, and they only lowered it to about 150/90.

[jgrumet]

I have no idea what the heck that says...I need to learn research language.

[caryn]

Jamie, I didn't do a terribly good job of translating it. Because I skipped the translating bit and went on to riff on how it connected to other stuff. :-)

It says that they found a protein that's probably produced by the mother's bloodstream to be elevated, and in a dose-response relationship to blood pressure (the higher the level of maternal endothelin-1, the higher the blood pressure.)

The women with generally higher levels also had a mutation in the gene that codes for that protein, the sort of mutation they call a "genetic polymorphism". (The funky clotting genes a lot of us have are also like this. We think of them as neutral mutations, because they show up in a substantial portion of the population and wouldn't do that if they usually killed people. Something like 30% of the Caucasian population carries the MTHFR mutation, and usually it doesn't seem to contribute to earlier death than the more common form of the gene.)

DNA is just four bases (A, C, T, and G), and one had been swapped just at point 5665 in the gene for endothelin-1 -- so we know exactly how this polymorphism looks.

So in the preeclamptics, maternal endothelin-1 was elevated and placental endothelin-1 was reduced. That's probably because it raises the mother's blood pressure and lowers the baby's. If the problem is poor blood flow into the placenta -- because the placenta's shallowly implanted -- then what the placenta does is turn up the pressure on the mother's side by increasing levels of production of this protein, and turn it down on the baby's side by decreasing it, so that blood is being pushed across the interface and then, once it gets to the baby's side, there's no obstacle at all to free flow. I think of it as a gradient, like the body is trying to make a waterfall by lifting the mother's side and lowering the baby's side.

And that is very likely an adaptive response to the condition of poor blood flow encountered by the placenta. When it detects a problem with poor blood flow (probably when it runs short of oxygen it throws multiple biochemical switches on in response), the placenta manipulates the maternal blood pressure and the fetal blood pressure to maximise blood flow to the baby given the shallow implantation.

As we say, evolution is smarter than you are. :-)