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A new gene trigger for pregnancy disorder identified
Date:5/11/2008

BOSTON The COMT gene known already for its role in schizophrenia has been found to play a role in preeclampsia, according to a report in todays advance on-line issue of Nature.

Led by researchers at Beth Israel Deaconess Medical Center (BIDMC), the study further suggests that a steroid molecule, 2-ME, may serve as both a diagnostic marker and therapeutic supplement for the treatment of this dangerous pregnancy disorder.

Characterized by hypertension, proteinuria, and edema, preeclampsia affects approximately 5 percent of all pregnancies worldwide, and is a leading cause of maternal and neonatal morbidity. Knowing that placental hypoxia, or oxygen shortage, associated with vascular dysfunction, is a hallmark of the condition, senior author Raghu Kalluri, PhD and his colleagues began by screening for genes that regulate hypoxia.

Seeing pregnant women with this disease in the clinic inspired me to dedicate our efforts to find likely causative genes that play a role in preeclampsia, says Kalluri.

During pregnancy, hypoxia is associated with the formation of new blood vessels, explains Kalluri, Chief of the Division of Matrix Biology at BIDMC and Professor of Medicine at Harvard Medical School.

As a result, during the first trimester of pregnancy, when the fetus is undergoing rapid development, hypoxia levels are high. As the pregnancy progresses, hypoxia levels should naturally come down as fetal blood vessels formation slows. But, he adds, for unknown reasons, patients with preeclampsia remain hypoxic well into their third trimester of pregnancy.

Studies in the Kalluri laboratory revealed an enzyme known as COMT (catechol-O-methyltransferase) in preeclampsia, a gene commonly associated with schizophrenia which, under normal circumstances, inactivates the catecholamine class of neurotransmitters.

Interestingly, this enzyme contributes to the breakdown of estrogen into 2ME (2-methoxyestradiol), a me
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Contact: Jerry Berger
jberger@bidmc.harvard.edu
617-667-7308
Beth Israel Deaconess Medical Center
Source:Eurekalert

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