Health
Indian origin scientist identifies new gene trigger for preeclampsia
London | May 12, 2008 12:23:46 PM IST
A scientist of Indian origin and his team at Beth Israel Deaconess Medical Center (BIDMC), have identified a gene called COMT - commonly associated with schizophrenia - that plays a role in preeclampsia, a leading cause of maternal and neonatal morbidity. The team, led by senior author Raghu Kalluri, PhD, further suggests that a steroid molecule, 2-ME, might serve as both a diagnostic marker and therapeutic supplement for the treatment of this dangerous pregnancy disorder. Knowing that placental hypoxia, or oxygen shortage, linked to vascular dysfunction, is a hallmark of the condition; researchers 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," Nature quoted Kalluri, Chief of the Division of Matrix Biology at BIDMC and Professor of Medicine at Harvard Medical School, as saying. "During pregnancy, hypoxia is associated with the formation of new blood vessels. As a result, during the first trimester of pregnancy, when the foetus is undergoing rapid development, hypoxia levels are high. As the pregnancy progresses, hypoxia levels should naturally come down as foetal blood vessels formation slows," he added. However, he said that for unknown reasons, patients with preeclampsia remain hypoxic well into their third trimester of pregnancy. During the study, researchers identified an enzyme known as COMT (catechol-O-methyltransferase) in preeclampsia, already known to play a role in 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 metabolite that suppresses the activity of hypoxia inducible factor protein," Kalluri said. "We wondered if, in cases of preeclampsia, COMT was not functioning properly. In support of this hypothesis, we found that COMT levels were deficient and 2-ME levels were lower in pregnant women with preeclampsia," he added. Researchers then looked at genetically engineered COMT deficient mice and found that the animals failed to produce 2-ME. At 14 weeks gestation, the presumable equivalent of the beginning of the third trimester in human pregnancy, the animals developed protein leak in the urine, high blood pressure and problems with placental blood vessels linked to decreased oxygen levels. Besides this, the researchers found that the animals delivered a day or so earlier than normal pregnant mice and there was a greater incidence of stillborn pups. However, once the pups were delivered, the health of the mother returned to normal. "The loss of 2-ME likely sets in motion a cascade of events culminating in preeclampsia. Disruption of COMT/2-ME led to elevated hypoxia, leading to angiogenic dysfunction and placental insufficiency, which then results in a further decrease in 2-ME levels," Kalluri said. In the final segment of the study, the authors administered 2-ME to the mice, resulting in a reversal of preeclampsia-like-symptoms. "Interestingly, the many diverse factors that have been identified in the recent years as elevated or suppressed in women with preeclampsia are fixed by 2-ME, suggesting that this action of COMT is central to proper vascular function in the placenta. This study offers the possibility of screening for COMT gene defects in pregnant women to predict preeclampsia," Kalluri said. The study was published in advance on-line issue of Nature. (ANI)
Balmiki delegation meets Ambala range IG President in Pune; talks about India, Gandhi BJP nets three MLAs from opposition parties Rajde Trust to give away scholarships to young cricketers
| 
