A Yale research team led by Richard P. Lifton, M.D., professor of genetics, medicine, and molecular biophysics and biochemistry, has identified the molecular cause of an inherited form of hypertension in pregnant women.
"We investigated a family with unusually severe hypertension and David Geller, one of our team members, discovered a mutation in the mineralocorticoid receptor gene in this family," said Lifton. "We demonstrated that this mutation causes a new form of hypertension that is exacerbated by pregnancy."
Hypertension that develops or worsens with pregnancy complicates about six percent of all pregnancies and is a major public health problem, contributing to pre-eclampsia, a hypertensive disorder of pregnancy that increases both fetal and maternal morbidity and mortality. The causes are largely unknown.
A steroid called aldosterone normally activates the mineralocorticoid receptor, Lifton said, increasing salt balance and raising blood pressure. When women with this mutation become pregnant, the 100-fold increase in progesterone b -- a normal hormone of pregnancy -- can also activate this receptor, causing increased salt balance and marked worsening of hypertension.
"Our findings demonstrate that a normal hormone of pregnancy can have abnormal effects that can cause hypertension to worsen and raises the possibility that more common forms of pregnancy-related hypertension may be attributable to similar mechanisms," Lifton said.
The findings, he said, will motivate careful examination of the possibility that progesterone is acting to promote increased salt balance in other forms of pregnancy-related hypertension.
"These findings may lead to clinical trials of salt restriction in selected groups of women whose blood pressure rises with pregnancy," said Lifton.
Lifton's team included David S. Geller, first author on the study, Anita Farhl, Nikki Pinkerton, Michael Fradley, Michael Moritz, Adrian Spitzer, Gretchen Meinke, Francis T.F. Tsal and Paul B. Sigler, M.D.
Journal
Science