Genetic risk of pre-eclampsia in pregnancy

A major international study has revealed for the first time how a baby’s DNA can increase the risk its mother will develop pre-eclampsia – a potentially lethal condition for both mother and child.

The five year investigation - which involved a team from the University of Leeds - raises the possibility that scientists will be able to develop better ways of predicting women at risk of the condition.

Professor James Walker, from the Leeds Institute of Biomedical and Clinical Sciences and lead obstetrician in the study, said: “We have suspected for some time that there is a genetic link with pre-eclampsia but until now we have not been able to understand how that link might work.

“This research is revolutionising our understanding of a common and serious complication of pregnancy.”

Pre-eclampsia affects around one in 20 pregnancies and is first suspected when a woman is found to have high blood pressure, usually in the second half of pregnancy. The condition can cause serious complications including fits, stroke, liver and blood problems and in extreme cases, the death of mother and baby. 

The condition is caused by faulty formation of the placenta, the organ that forms in the woman’s uterus and provides oxygen and nutrients to the developing baby.

It is the baby’s DNA that controls the way the placenta develops, so researchers looked there for possible clues that genetic factors played a role in pre-eclampsia.

The study, published in Nature Genetics, involved comparing the genetic make up of 4,380 babies whose mothers had pre-eclampsia with the DNA of more than 300,000 healthy babies.

The investigators found variations close to a gene that makes a protein called sFlt-1. When high-levels of that protein are produced and leave the placenta and enter the mother’s bloodstream, she is at risk of developing high blood pressure, damage to kidneys, the liver and brain – which are all features of pre-eclampsia.

The investigators concluded that these genetic variants put the mother at an increased chance of developing pre-eclampsia.

Detailed analysis of the DNA was conducted at the Wellcome Trust Sanger Institute in the UK and deCODE Genetics  in Iceland.

Dr Ralph McGinnis, who led the analysis at the Sanger Institute, said: “Pre-eclampsia has been recognised since ancient Egypt and Greece as being a danger to the lives of mothers and babies.  This first piece of the genetic jigsaw holds substantial promise for unlocking some of the mystery of how pre-eclampsia is caused. 

“Our finding may also enable better prediction of mothers who will become pre-eclamptic when combined with clinical information and with other pieces of the genetic jigsaw that will also surely be discovered in the next few years.”

The investigators acknowledge that although genetic variations increase the risk of pre-eclampsia, it is not the whole story.

The DNA changes associated with pre-eclampsia are common – over 50% of people carry this sequence in their DNA so the inherited changes are not sufficient in themselves to cause the disease. There are other, as yet undetermined, factors at work.

Further information

This research was funded by a six million Euro grant from the European Commission.

DNA from a further 4,220 babies from pregnancies where the mother suffered pre-eclampsia have been collected in Kazakhstan and Uzbekistan in a project developed and coordinated by Professor Walker and his team - Dr Nigel Simpson and Ms Viv Dolby. These samples are currently being analysed in an extended study to see if the same variations occur near sFlt-1.

Journalists requiring more information or with interview requests relating to this story should contact David Lewis in the University of Leeds press office on 0113 343 8059.