Genetic study shows that the risk of pre-ecla
Preeclampsia, usually diagnosed by increased blood pressure and protein in the urine, affects up to 5% of pregnant women. Globally, it contributes to the deaths of around 50,000 women and up to one million babies each year. The disease is also associated with an increased risk of cardiovascular disease in mothers and their children later in life. There is a hereditary risk, as women with a family history of preeclampsia are at greater risk of developing the disease themselves.
In the InterPregGen study, researchers from the UK, Iceland, Finland, Norway, Denmark, Kazakhstan and Uzbekistan investigated how maternal genetic variation influences risk for preeclampsia. The team studied the genetic makeup of 9,515 preeclampsia women and 157,719 control individuals.
The results, published today in Nature Communication, identified DNA variants in the ZNF831 and FTO genes as risk factors for preeclampsia. These genes have already been associated with blood pressure, and the FTO variant also with body mass index. Further analysis revealed other blood pressure related variants in the MECOM, FGF5 and SH2B3 genes also associated with preeclampsia. These variants increase the risk of preeclampsia by 10 to 15%.
The study also shows that the overall genetic predisposition to hypertension is a major risk factor for preeclampsia and therefore a large number of variants each with a small effect may also contribute to the risk. These current findings complement earlier findings by the same researchers, who showed that a variant close to the FLT1 gene in the fetal genome affects mothers’ risk of developing preeclampsia.
The genes identified so far go hand in hand with other current knowledge about preeclampsia, as hypertension and obesity are known maternal risk factors. This study shows that these associations are partly explained by hereditary predispositions. However, they only explain part of the risk of preeclampsia. It remains to be seen whether the remaining unidentified factors act across the maternal or fetal genome, or both.
New knowledge from this study could form the basis for more effective prevention and treatment of preeclampsia in the future, and improve pregnancy outcomes for mother and child.
The five-year study was coordinated by Dr Linda Morgan of the School of Life Sciences at the University of Nottingham; Nottingham professors emeritus Noor Kalsheker (clinical chemistry) and Fiona Broughton Pipkin (obstetrics and gynecology) were among the collaborators.
Professor Fiona Broughton Pipkin said: “The new information from this study may form the basis for more effective prevention and treatment of preeclampsia in the future, and improve pregnancy outcomes for the mother and child. ”
“They could also encourage general practitioners to follow more closely women who have had pre-eclampsia.”
The full study is published here and was funded by a EUR 6 million grant from the European Commission.
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