Research may help physicians identify women with an increased risk of developing pre-eclampsia early in pregnancy through genetic and metabolic screening

An international team of researchers has identified a gene that may play a role in pre-eclampsia, a condition that can occur during pregnancy that can affect both mother and unborn infant, according to findings published in the May 11 advance online issue of Nature.

The findings may one day help physicians identify women with an increased risk of developing pre-eclampsia early in pregnancy through genetic and metabolic screening. Additionally, it could lead to the development of therapeutic interventions and preventative measures to reduce the risk of developing pre-eclampsia, the major symptom of which is high blood pressure. Pre-eclampsia is a major cause of premature deliveries. Currently, there is no way to predict which women will develop the condition.

Worldwide pre-eclampsia affects between 5 percent and 8 percent of pregnancies and is characterized by high blood pressure and an excess of protein in the urine. Typically diagnosed after 20 weeks of pregnancy, pre-eclampsia can be fatal for mother and infant if left untreated and once developed, the only cure is delivery.

The team, led by researchers at Beth Israel Deaconess Medical Center, included Jerome F. Strauss III, M.D., Ph.D., dean of the Virginia Commonwealth University School of Medicine, and colleagues at the University of Birmingham, in the United Kingdom, the University of Pennsylvania School of Medicine, the University of Heidelberg in Germany, the Indiana University School of Medicine and Children's Hospital Boston.

"These findings open up new avenues for thinking about the path of physiology of pre-eclampsia, its diagnosis and treatment," said Strauss.

Researchers found that the COMT gene is associated with pre-eclampsia. The COMT gene produces a compound known as 2 methoxyestradiol, which regulates the body and prevents it from entering a hypoxic state. Levels of 2 methoxyestradiol increase as pregnancy progresses and can be easily measured in blood and urine of pregnant women. Researchers said that low levels could indicate that COMT is not producing adequate amounts of 2 methoxyestradiol, which could result in pre-eclampsia.

The team examined mice that did not have the COMT gene and observed that these mice developed pre-eclampsia. However, when they were given 2 methoxyestradiol, symptoms of pre-eclampsia – high blood pressure and problems with the blood vessels of the placenta associated with hypoxia – were reversed.

At VCU, Strauss together with Lori Hill Walsh, an M.D./Ph.D. candidate, recently presented findings that a polymorphism or genetic variant in the fetal COMT gene is associated with pre-eclampsia, providing additional evidence that the gene plays a role in human pre-eclampsia.

"We found that human fetuses that have a certain variant of the COMT gene are associated with a higher risk of the mom developing pre-eclampsia. Therefore, it's a problem in the fetus that causes the mom to develop pre-eclampsia," said Walsh.

"In the future, the findings may lead to the development of genetic testing or, even easier, screening of pregnant women for low levels of 2 methoxyestradiol in their blood or urine. If this problem is recognized early in pregnancy, physicians could supplement these mothers with 2 methoxyestradiol and prevent their pre-eclampsia," she said.

This work was supported by grants from the National Institutes of Health, the British Heart Foundation and the Kanae Foundation for the Promotion of Medical Science in Japan.

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Virginia Commonwealth University