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Single genetic defect links many risk factors for heart disease and stroke

For the first time, researchers have demonstrated that a single change in a person's DNA can contribute to a range of life-shortening risk factors, including high blood pressure, high cholesterol, and other metabolic disorders.

The mutation affects the genes of the mitochondria the energy-producing power plants of the cell that are passed from mother to offspring. The researchers are hopeful their discovery could help unravel the complex genetic and environmental factors that cause a range of metabolic disorders.

The researchers, led by Howard Hughes Medical Institute investigator Richard P. Lifton, who is at Yale University School of Medicine, published their findings October 22, 2004, in Science Express, an online component of the journal Science. Gerald I. Shulman, another HHMI investigator at the Yale School of Medicine, was also an author on the paper.

"Epidemiological studies over the last twenty years have shown that hypertension, high cholesterol, high triglycerides, low magnesium, diabetes, insulin resistance, and obesity tend to cluster with one another, but not in a simple way," said Lifton. "Not everybody who has any one of these traits has all of the others. The pattern of inheritance is complicated, and there hasn't been a clear understanding of what's driving this relationship."

Various combinations of these abnormalities affect up to a quarter of the U. S. population, and they are contributing to a public health epidemic of heart disease and stroke.

Lifton said that one woman with hypertension and low blood magnesium levels proved to be the key to tracing the genetic cause of the array of pathologies. Since low magnesium occurs infrequently in the general population, the researchers tested her for known mutations that they had previously associated with that trait.

"When we spoke to her, what stood out was that she said that a number of other family members also had low magnesium," said Lifton. "Tha
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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
21-Oct-2004


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