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Scientists Spot Stroke Genes
Date:4/15/2009

Chromosomal region contains two suspect variants that raise risk for brain attack

WEDNESDAY, April 15 (HealthDay News) -- Scientists have identified a chromosomal region that may contain two genetic variants responsible for an increased risk of ischemic stroke.

About 20 percent of whites and 10 percent of blacks in the United States and Europe have at least one copy of the genetic variant. Each variant increases the risk of this type of stroke by 30 percent, according to the authors of a study being published online Wednesday and in the April 23 print issue of the New England Journal of Medicine.

The hope is that this discovery will one day translate into new treatments and ways to prevent the most common type of stroke.

"You need to start with something, and having this information allows you to try to attempt to look at prevention," said Dr. Keith Siller, medical director of the Comprehensive Stroke Care Center at New York University Langone Medical Center. "It may not mean anything now, but how can you even begin to tackle prevention of this disease if you don't know what causes it. This is a very important initial step."

Siller was not involved with the study, which was funded by the National Heart, Lung and Blood Institute and other arms of the National Institutes of Health.

The eventual implications are potentially enormous.

Ischemic stroke, caused by blocked blood flow to the brain, accounts for almost 90 percent of all strokes.

"Stroke is the number three cause of death and the leading cause of disability," Siller said. "We're talking about millions and millions of people who have some sort of genetic predisposition."

Research on stroke has traditionally focused more on lifestyle factors.

"There hasn't been very much known about specific genes in stroke," Myriam Fornage, co-author of the study and a cardiology professor at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at the University of Texas Health Science Center at Houston. "Stroke has traditionally been a little bit behind, so this is a nice breakthrough in that regard because we're sort of catching up."

The authors used data from a consortium of four studies involving almost 20,000 people, all white, followed for an average of 11 years.

"Basically, the studies were monitoring the development of stroke over time, and we superimposed onto that information the genetic data, which was to look at 2.2 million polymorphisms across the genome in these participants," Fornage explained. "We identified two polymorphisms that were located in the same chromosomal region."

The researchers replicated the findings in other white populations and in blacks.

"What we have now is a location for a gene that predisposes to stroke," Fornage said. "We still don't know the actual mutation, [although] we have a good idea that it's the NINJ2 gene, involved in the brain's response to injury." The other gene candidate is WNK1, involved with blood pressure control.

Researchers next need to understand how the genes work.

"The step is to identify the actual mutation that may occur in that gene," Fornage said.

Siller said that researchers are "getting closer and closer to unraveling certain recipes in the body for what might predispose you to stroke."

"But unless you can manipulate the genes, the information is not practical, but that doesn't mean we shouldn't get this information," he said. "We have to gear up for the time manipulations might be possible."

Also, being able to identify people at greater risk for stroke might spur more aggressive lifestyle changes in order to reduce that risk, Siller added.

"That does have implications for today," he said.

More information

The American Stroke Association has more on ischemic stroke.



SOURCES: Myriam Fornage, Ph.D., Laurence & Johanna Favrot Distinguished Professorship in Cardiology, Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston; Keith Siller, medical director, Comprehensive Stroke Care Center, New York University Langone Medical Center, and assistant professor of neurology and psychiatry, New York University School of Medicine, New York City; April 23, 2009, New England Journal of Medicine


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