New genetic insight into preeclampsia

22 June 2017

PREGNANT-WOMAN

A pregnant woman

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A genetic link has been found to preeclampsia, the condition that causes high blood pressure and urinary protein in a pregnant mother and retards the growth of her developing baby.

About 1 in 20 pregnancies are affected by preeclampsia, usually in the later stages of the pregnancy, and, worldwide, it's a leading cause of maternal death.

In developed countries doctors tend to be very good at managing the condition, which resolves completely as soon as the baby is born, but, nevertheless, the diagnosis is sometimes made too late and there are already health consequences by the time preeclampsia is picked up.

Previously scientists have tried unsuccessfully to link the genetic makeup of the mother to the risk of developing the condition. This prompted Sanger Institute researcher Ralph McGinnis and his colleagues to try an alternative tack. Rather than interrogate the genomes of affected mothers, they elected to test the DNA of babies born to affected mothers.

Writing in Nature Genetics, the team carried out a test called a Genome-Wide Association Study or GWAS. This involves taking a large group of unaffected "control" individuals and comparing the pattern of inherited DNA markers called single nucleotide polymorphisms or SNPs in their genomes with DNA collected from a group of affected individuals.

The rationale behind the approach is that if a certain DNA region is linked to a disease then the same SNP markers will crop up repeatedly in the affected group but much less often in the healthy control group.

In the current study the researchers considered over 7 million SNPs in the DNA sequences of more than 300,000 healthy babies. They compared this data with the SNP profiles of 4380 babies whose mothers were diagnosed with preeclampsia during their pregnancy.

This approach yielded a hit in one part of chromosome 13 close to a gene called FLT-1. This gene encodes a receptor that detects the presence of growth factors in the placenta, which is the structure that links to baby to the wall of the mother's uterus and controls the flow of nutrients into the baby and the return of waste to the mother.

The levels of the gene product, called sFlt-1, are indeed higher in the blood of mothers affected by preclampsia compared with healthy pregnancies. This excess of sFlt-1, the researchers speculate, is what causes the lining of the mother's blood vessels to begin to behave abnormally, triggering the tendency to hypertension and kidney damage.

Commenting on the work, Cambridge University obstetrician and researcher Catherine Aiken points out that "it's a really interesting observation because it's opening a door on how this very common - but very poorly understood - condition of preeclampsia occurs."

At the moment there is no test to pinpoint who might be at risk of developing the condition. "This isn't that test," says Aiken, "but it's a first step towards one day us having a screening tool to pick up those women who need closer monitoring as their pregnancy progresses."

At the very least the work spotlights for the first time a potential mechanism for how preeclampsia happens.

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