Suspect is protein made by the fetus and needed to form placenta’s blood vessels
A protein made by the fetus may lead to preeclampsia in moms.
People born to mothers who had the prenatal disorder were more likely to have certain DNA variations near a gene known to influence blood vessels. The results, published online June 19 in Nature Genetics, point to that gene as a possible preeclampsia culprit, and may help scientists develop ways to stop or prevent the pregnancy complication. Preeclampsia, which is marked by a dangerous spike in blood pressure, affects about 5 percent of pregnancies and is estimated to kill over 70,000 women a year globally.
Scientists have known that preeclampsia can run in families, but the genetics of the fetus hadn’t been scrutinized. “Over the years, people have looked at mothers’ genes,” says geneticist Linda Morgan of the University of Nottingham in England. “This is the first large study to look at babies’ genes.”
Morgan and colleagues compared DNA variations in 2,658 babies, children and adults born to mothers who had preeclampsia with those in more than 300,000 people. (This large group probably included some people born to mothers with the condition, but the vast majority were not.)
A genome-wide association study (GWAS), a technique used to comb through DNA looking for genetic variations that may be linked to a disorder, pinpointed a spot on chromosome 13, near a gene called FLT1. That gene is involved with blood vessel formation, an intricate process for the placenta as it grows into the inside wall of the uterus and merges the baby’s blood supply to the mother’s. The same genetic hot spot turned up in tests of a second group of offspring from mothers who had preeclampsia, Morgan and colleagues report. Another DNA variation near the gene also showed a link to the disorder.
Identifying FLT1 “makes a lot of sense,” says Ananth Karumanchi, a vascular biologist at Beth Israel Deaconess Medical Center in Boston, who was not involved in the study. Earlier experiments by Karumanchi and others suggest that the gene plays a role in preeclampsia.
Preeclampsia is kicked off by the placenta, an organ grown mostly from fetal cells that helps provide nutrients to the fetus. And though the details are unclear, some scientists suspect that unhealthy placentas start to pump out too much Flt-1 protein. A version of the protein called sFlt-1 can then slip into a mother’s bloodstream, where it may damage blood vessels in a way that leads to high blood pressure.
The GWAS results can’t explain the bulk of preeclampsia cases. A fetus carrying a single copy of one of the troublesome variants near FLT1 raised a mother’s risk of preeclampsia by about 20 percent, the analysis suggests. Other risk factors are known to be much stronger, Morgan says, including previous high blood pressure, former preeclampsia diagnoses or carrying twins.
Karumanchi says that the genetic results might not be strong enough on their own to make the case that the gene is involved. But other work points to FLT1. “We feel it’s the right target,” he says.
In Europe, a preliminary clinical trial is testing a filtration method that removes excess sFlt-1 protein from the blood of women with signs of preeclampsia. So far, about 20 women have undergone the procedure, says nephrologist Ravi Thadhani of Massachusetts General Hospital in Boston. Early results are “quite encouraging,” he says, and he hopes to expand the study soon.
R. McGinnis et al. Variants in the fetal genome near FLT1 are associated with risk of preeclampsia. Nature Genetics. Published online June 19, 2017. doi:10.1038/ng.3895.
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