pressure point. Region bind steroids (green) mineralocorticoid receptor. A mutation in the receptor results hypertension.
One in five Americans and Europeans has high blood pressure, a dangerous disorder with many genetic causes are only now being revealed. Now a team of researchers has discovered an important piece of the puzzle: a genetic mutation that leads to early onset hypertension. The mutation may help explain the causes of the most common forms of hypertension and may also explain why blood pressure of some women increases significantly during pregnancy.
The team, led by geneticist Richard Lifton of Yale Medical School, had earlier linked a series of genes with abnormal blood pressure. Finding new mutations in the genes that cause hypertension, they routine screening of patients with hypertension. Among them was a 15 year old boy with severe hypertension. The researchers discovered that he had a mutation in the mineralocorticoid receptor, a protein in the kidney cells that is involved in the handling of the salt body. When activated by the steroid hormone aldosterone receptor that normally triggers a cascade of molecular events that cause kidney cells to absorb salt and water for release back into the blood. This can help prevent dehydration on a hot summer day, but it also raises blood pressure.
Lifton and his colleagues then found that the mutation caused the hypertension before age 20 in all parents of the boy who had inherited. They found the reason for the engineering of cells in culture to shine when the mineralocorticoid receptor has been activated. The modified cells with the mutant receptor shone all the time - even in the absence of aldosterone. The mutant receptor seems to be permanently stuck in the "on" position, Lifton and colleagues report in the July issue 7 Science .
To their surprise, they also found that progesterone, which clog the normal receptor, strongly stimulated the mutant version. Because progesterone levels increase dramatically during pregnancy, Lifton wondered whether the hormone aggravate the blood pressure problems in pregnant women who have this mutation. EMail: Worsening hypertension had hit five pregnancies of two women carrying the mutated receptor. Lifton do not think that this particular mutation will prove to be common. But he says the results suggest that the salt recycling pathway, in which the acts of mutant receptors may be important in hypertension. They also suggest that hormones such as progesterone could in certain cases hyperstimulate track.
"It is a real tour de force," says nephrologist Friedrich Luft of the Max Delbrück Center for Molecular Medicine in Berlin, Germany. "He discovers new and unexpected mechanisms for hypertension" in humans, he said, which could one day lead to better treatments and new diagnostic tools for the disease.
Related Sites
Richard Lifton
Lifton laboratory
Information on hypertension National Institutes of Health
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