Researchers at NTNU have contributed to the discovery of gene variants in mothers that increase their risk of both preeclampsia and heart disease.
NTNU is part of the large international research project InterPregGen. The project was the first in the world to discover gene variants in foetuses that predispose mothers to preeclampsia.
Now the project has also identified several gene variants in mothers who are predisposed to preeclampsia. It turns out that the same gene variants are associated with cardiovascular disease and obesity.
“The findings indicate that there’s a close, and hereditary, connection between these diseases. The risk of getting heart disease later in life is doubled for women who’ve experienced preeclampsia. For mothers who have been through severe and repeated preeclampsia, the risk of heart disease is even higher,” says Professor Ann-Charlotte Iversen at NTNU.
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Genetics confirms disease research
Researchers know from previous epidemiological health studies in the population – including the Trøndelag Health Study (HUNT) – that women who have had preeclampsia more often develop heart disease later in life.
Research has also shown that certain gene variants contribute to the development of heart disease.
“If you’ve experienced preeclampsia, the risk of a recurrence increases.”
“The new thing is that we’ve found clear genetic links between preeclampsia and heart disease. This brings us closer to understanding what’s important in the development of both diseases. Especially to understanding the causes of preeclampsia,” says Iversen.
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No good treatment – yet
Preeclampsia is complex and involves a disease of the placenta and the mother’s response to this condition.
“More insight can help us to better predict the disease, find a good treatment and know who needs follow-up with regard to the risk of cardiovascular disease,” Iversen says.
“Today, high-risk women receive small doses of acetylsalicylic acid, and antihypertensive therapy can reduce symptoms, but we can’t yet offer effective treatment,” she said.
What’s especially problematic with preeclampsia is that the disease can’t be detected until the mother shows signs of illness in the latter part of her pregnancy. High blood pressure and protein in the urine are the most typical symptoms.
“Preeclampsia is a disease in which the father’s genes also play a role.”
Other possible symptoms are organ failure, headaches, visual disturbances and motor restlessness. The disease often starts much earlier in the pregnancy with poor placental function.
If preeclampsia occurs before week 34, it often results in inhibited foetal growth and more severe symptoms for the mother.
“If preeclampsia occurs after week 34, the symptoms are milder but can in some cases become more serious. If you’ve experienced preeclampsia once, the risk increases that it will recur in subsequent pregnancies. Fortunately, examinations can detect the signs through the pregnancy tests that all pregnant women in Norway are offered,” says Iversen.
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Talk to your doctor
The professor believes it’s important for women who have experienced preeclampsia to be aware of their greater risk of developing heart disease later in life.
“This risk applies especially to women who’ve had severe preeclampsia. That’s when preventive lifestyle measures kick in. Talk to your doctor. The problem is that getting the younger population to think preventively about lifestyle at such an early age can be difficult.
Father’s genes also important
Preeclampsia is a disease in which the father’s genes also play a role.
“We already know that men who were born to mothers with preeclampsia have an increased risk of the same thing happening to their own children. The foetus is a mixture of maternal and paternal genes, and the foetal cells are primarily what make up the placenta. The foetal genes, including the paternal ones, are therefore crucial,” Iversen said.
The second aspect of the disease development involves how the mother’s body handles the stress signals from the placenta when it’s not working properly. Certain gene variants in the mother may worsen her response to dealing with a less well-functioning placenta, so that she could develop preeclampsia.
NTNU is one of twelve partners from six countries in Europe and Central Asia participating in the InterPregGen project.
Iversen points out that a large data base is a prerequisite for researching such a complex genetic disease. Iversen is a professor at NTNU’s Department of Clinical and Molecular Medicine and the Centre of Molecular Inflammation Research (CEMIR) at NTNU.
Gynaecologist and researcher Liv Cecilie Vestrheim Thomsen at the University of Bergen has played a central role in the genetic research.
Approximately three per cent of women giving birth in Norway develop preeclampsia. The disease can be life threatening for both mother and child, but in this country deaths very rarely occur due to preeclampsia. No effective treatment currently exists.
Reference: Steinthorsdottir, V., McGinnis, R., Williams, N.O. et al. Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women. Nat Commun11, 5976 (2020). https://doi.org/10.1038/s41467-020-19733-6