Gene to blame for deadly pregnancies
- Gene to blame for deadly pregnancies* 14 May 2008* From New Scientist Print Edition. Subscribe and get 4 free issues.* Ewen CallawayA LIFE-threatening complication that strikes in 5 per cent of pregnancies was once dubbed the "disease of theories". Now the discovery that mice missing a specific gene develop pre-eclampsia could lead to a treatment for women.A major cause of premature births, pre-eclampsia can strike as early as 20 weeks into pregnancy and kill both mother and child. Women develop high blood pressure and their kidneys start to fail. The only treatment is to deliver the baby, often weeks early. Abnormal blood vessel growth, which starves the placenta of oxygen, has been blamed, but it is unclear what sets this off. "It's one of the biggest mysteries in medicine," says Raghu Kalluri of the Beth Israel Deaconess Medical Center in Boston.Now Kalluri's team says at least some cases of pre-eclampsia could be caused by mutations in a gene that helps produce the chemical 2-methoxyoestradiol (2-ME), which helps control blood vessel growth. "The difference sets the ball rolling and a million other things downstream go wrong," he says.“If the effect is the same in humans, detecting 2-ME could help diagnose pre-eclampsia, while extra doses could treat it”Pregnant mice lacking the gene have protein in their urine, a sign of kidney failure, and elevated levels of two proteins that are present in the blood of women with pre-eclampsia. These mice are also more likely than ordinary mice to have premature births, high blood pressure and problems forming blood vessels in the uterus and placenta. Extra doses of 2-ME reversed many of the symptoms (Nature, DOI: 10.1038/nature06951).If 2-ME has the same effects in humans, detecting low levels in the blood could help diagnose pre-eclampsia, while giving extra doses could help treat it. The "wonderful thing" about 2-ME is it is present in high levels during pregnancy anyway, says Kalluri. "It's not like we are giving anything that the baby and the mother aren't exposed to."The team has already discovered that 13 women with pre-eclampsia had lower levels of 2-ME in their blood before giving birth than women who had normal births. Now they plan to study pregnant women with genetic mutations that hamper 2-ME production. "In some patients, this may well be important," says pre-eclampsia expert James Roberts of the University of Pittsburgh in Pennsylvania. However, one gene alone is unlikely to cause all cases of pre-eclampsia.