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Gene May Be Key to Pregnancy Complication
Date:5/12/2008

Preeclampsia is common and serious, but genetics could bring screening test or treatment

MONDAY, May 12 (HealthDay News) -- A gene called COMT, already known for its role in schizophrenia, also plays a significant part in the dangerous obstetric complication known as preeclampsia, a new study finds.

Although the current study was done in mice, the researchers envision a time when the findings could be used as a test to identify women at risk of preeclampsia -- and even as a means of preventing the condition.

"This gene regulates the oxygenation of the placenta," explained lead researcher Raghu Kalluri, a professor of medicine at Harvard Medical School. "Preeclampsia is a pregnancy disorder where the placenta is hypoxic (isn't receiving enough oxygen)," he added.

Preeclampsia, which affects about 5 percent of all pregnancies, is a leading cause of sickness for pregnant women and their infants. Symptoms of preeclampsia include high blood pressure, protein in the urine and swelling.

The COMPT (catechol-O-methyltransferase) gene is involved in breaking out estrogen into a metabolite called 2ME (2-methoxyestradiol), which prevents a shortage of oxygen in the placenta. When the gene does not function properly, levels of 2-ME are reduced, setting in motion a series of events that lead to preeclampsia, Kalluri explained.

The report was published online in the May 12 issue of Nature.

In their current experiments, the researchers worked with mice that did not have the COMT gene, and therefore do not produce 2-ME. After 14 weeks of gestation -- equivalent to the third trimester of human pregnancy -- the mice developed high blood pressure and other symptoms of preeclampsia, the researchers found.

The mice also delivered their pups earlier than normal, with a high incidence of stillborn offspring. Once the pups were delivered, the mother's health return to normal, the researchers found.

However, when the mice were given supplemental 2-ME, symptoms of preeclampsia disappeared, Kalluri said.

Kalluri's team found that COMT levels were deficient, and 2-ME levels were also lower, in women diagnosed with preeclampsia.

Because 2-ME is found in the blood and urine, the researchers hope to use their finding to develop a urine test that would identify women at risk from preeclampsia, Kalluri said. "This can be designed as a urine strip test, like pregnancy tests are," he said.

In addition, giving 2-ME to women who have low levels of this protein may prevent them from developing preeclampsia, Kalluri said. "We can give back the missing amount to bring levels back to where they should be," he said.

One expert believes the results are promising, but said more work is needed before 2-ME could become either a screening test or treatment.

"This is an interesting and novel study, which gives insight into the pathophysiology of preeclampsia," said Dr. Arun Jeyabalan, an assistant professor in the division of maternal fetal medicine in the department of Obstetrics, Gynecology and Reproductive Sciences at Magee Women's Hospital, University of Pittsburgh.

Jeyabalan said that it will be sometime before these findings can be extended to patients. Using these findings to develop a screening test is something worth looking into, she added.

"Most of this work is of animals, and I think we have to be cautious before we extend these findings to humans," Jeyabalan said. "But it is something that is definitely worth testing in the future."

More information

For more about preeclampsia, visit the U.S. National Library of Medicine.



SOURCES: Raghu Kalluri, Ph.D., professor,medicine, Harvard Medical School, Boston; Arun Jeyabalan, M.D., assistant professor, division of maternal fetal medicine, department of Obstetrics, Gynecology and Reproductive Sciences, Magee Women's Hospital, University of Pittsburgh; May 12, 2008, Nature


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