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Stroke Risk Higher with Gene Variations

Specific genetic variations have been linked to an increased risk of stroke in younger women, according to a University of Maryland researchers which has added to the growing evidence of possible genetic influences in stroke. //

The study results, which appear in the August issue of Human Molecular Genetics, indicate an increased risk ranging from 50 to 100 percent depending on the particular genetic variation.

"This finding is another important step in understanding the role genes may play in stroke," says study author John W. Cole, M.D., M.S., a research staff physician at the Baltimore Veterans Affairs Medical Center and an assistant professor of neurology at the University of Maryland School of Medicine.

He adds, "We have verified that specific variations, or polymorphisms, that occur within a particular gene are associated with increased stroke risk; now we need to explore why. With a better understanding of these polymorphisms, we may someday develop a genetic test to identify women who may be at greater risk of stroke. These women could receive more intensive screening and counseling for other stroke risk factors such as smoking, high blood pressure and the use of oral contraceptives."

The University of Maryland researchers looked for the genetic variations in a group of more than 400 African-American and Caucasian women between the ages of 15 and 49, half of whom had suffered an ischemic stroke (caused by a blood clot in the brain). Previous studies had linked variations in a specific gene, phosphodietsterase 4D (PDE4D), to an increased risk of stroke in populations of older men.

The Maryland group evaluated more than two dozen variations in the PDE4D gene and was the first to verify an increased risk of stroke in younger women. Five variants were found to be associated with increased stroke risk. The researchers also found that smokers who have one of these variants are at much higher risk and the mor e they smoke, the greater the chance of stroke.

The study participants are part of a research initiative called the Stroke Prevention in Young Women Study, which evaluates both genetic and non-genetic risk factors for ischemic stroke in young women. These women are from Maryland, Washington D.C., and portions of southern Pennsylvania and western Delaware.

The Stroke Prevention in Young Women study also provided the researchers with a control group for comparison purposes that consisted of women who had not suffered a stroke.

The new study also associated the genetic variations with stroke in both small and large blood vessels. And the researchers found the increased risk to be similar for both the African-American and Caucasian stroke patients. But, they say, more research is needed, including looking at a larger sample size and other population groups, before the concept can be applied to patient care.

"We want to know how these polymorphisms work. Do they cause the body to produce a defective protein or perhaps too much or too little of a particular protein? With more understanding, perhaps we can develop a genetic test that will help patients," says Dr. Cole, who also is a neurologist at the University of Maryland Medical Center.


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