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Eclampsia has puzzled doctors for more than two millennia: the seizures that characterise this condition were described as early as 400 BCE or so. The disorder that sets the stage for their onset is known as pre-eclampsia. The likelihood of developing this condition increases for women whose mother or sisters have had it, although family history is not the only factor involved.
“Pre-eclampsia is the most dangerous complication of pregnancy,” says Gulnara Svyatova of the Kazakh Ministry of Health’s Scientific Centre for Gynecology, Obstetrics and Perinatology. “It is a major cause of maternal and perinatal mortality in our country and worldwide.”
The Centre was 1 of 12 partners involved in the five-year project InterPregGen, which set out in November 2011 to shed new light on the genetic causes of pre-eclampsia. The project identified several variants associated with the disorder, some of which had already been linked to high blood pressure in general.
Its outcomes widen the scope to identify women at risk, prevent the development of the condition or detect it early, and provide effective ante-natal care, Svyatova explains. Worldwide, pre-eclampsia currently “leads to the deaths of around 40 000 women and almost 1 million babies per year,” the InterPregGen partners note. Improved understanding of the causes could help to save many lives.
Nursing a theory
InterPregGen, which was led by the University of Nottingham, was certainly not the world’s first attempt to elucidate the genetic causes of pre-eclampsia, Svyatova notes. However, she says, it represented a turning point in that it was the first to consider whether the baby’s genes might be of relevance.
InterPregGen’s findings indicate that they are. The problems arising in pre-eclamptic pregnancies originate from faulty development of the placenta, Svyatova explains. And the genes driving the development of the placenta, she adds, are primarily those of the baby.
Baby matters
A protein expressed by the implicated gene in the baby, and therefore in the placenta, appears to be central to the issue. “At high levels, this protein released from the placenta into the mother’s bloodstream can cause damage to her blood vessels, leading to high blood pressure and damage to her kidneys, liver and brain,” Svyatova notes. “All of these symptoms are features of pre-eclampsia.”
To pinpoint variants associated with pre-eclamptic pregnancies, InterPregGen studied the complete genomes of thousands of mothers and babies, along with genetic material from more than 300 000 individuals. This research was carried out on DNA notably collected in western Europe and in Central Asia, where pre-eclampsia is more than twice as common.
As part of the process, the project set up biobanks in Kazakhstan and Uzbekistan, which respectively hold DNA samples volunteered by 9 700 and 7 000 citizens of these countries.
It also contributed to the training of local experts in molecular genetics and bioinformatics, Svyatova notes. “Thanks to InterPregGen and our project partners abroad, we have a well-trained staff of geneticists, biostatisticians and researchers in personalised medicine in Kazakhstan,” she explains.
Involvement in the project has generated new international contacts for her institution and added to its visibility at home and abroad, she adds. InterPregGen’s approach and outcomes have helped to inform Kazakhstan’s national programme for personalised medicine, which is due to start in May 2018, Svyatova concludes.