National Institutes of Health Provides $1.1 Million Grant to Fund Study
Researchers at the University of Maryland School of Medicine have received a $1.1 million grant from the National Institutes of Health (NIH) to identify genes that may increase the risk of stroke in younger people and to determine whether smoking serves as a trigger to activate these genes.
“We’re not only searching for individual genes that play a role in causing stroke, but also looking at whether smoking modifies the effects of these genes. We know that smoking is a major risk factor for stroke for both men and women, particularly those who are age 49 or younger,” says Braxton D. Mitchell, Jr., Ph.D., M.P.H., the principal investigator who is a professor of medicine and of epidemiology and preventive medicine at the University of Maryland School of Medicine.
The study is one of six research projects announced today by the NIH’s Genes, Environment and Health Initiative, which provided about $5.5 million in grants. The other studies will look at genetic factors that influence the risk for other common disorders, such as glaucoma, prostate cancer and high blood pressure.
Scientists will use a new approach called a genome-wide association study, or GWAS, to rapidly scan up to 1 million genetic markers looking for common variations in DNA in a large group of stroke cases and a large group of controls without stroke. The technique is being used to track down genes associated with many common diseases, such as Type 2 diabetes, Parkinson’s disease and cardiovascular disease. Researchers believe the wealth of new information produced by these studies will ultimately enable physicians to develop personalized treatment plans for patients.
“The long-range goal of our research is to identify the genetic and environmental factors that make people more susceptible to stroke in order to develop more effective prevention and treatment strategies,” says Steven J. Kittner, M.D., M.P.H., a co-investigator of the stroke study who is a professor of neurology and of epidemiology and preventive medicine at the University of Maryland School of Medicine. Dr. Kittner is also a neurologist at the University of Maryland Medical Center and a staff physician and researcher at the Baltimore VA Medical Center.
Stroke is the third leading cause of death and the leading cause of major disability in the United States. In addition to smoking, other risk factors include high blood pressure and use of oral contraceptives by women.
In the first phase of the study, University of Maryland researchers will examine
DNA from 929 people who took part in studies on “young-onset” stroke
at the School of Medicine over the past 18 years. Another 936 cases will serve
as controls. The group includes men and women, whites of European descent and
African-Americans, all under the age of 49.
Researchers hope to identify gene variations, which are known as single nucleotide polymorphisms, or SNPs, that are most strongly associated with stroke and then test these SNPs in nearly 2,000 other young-onset stroke cases (and 1,199 controls) from nine other institutions participating in the International Stroke Genetics Consortium. These other centers are located throughout the United States as well as in other countries, such as Poland, Sweden and England.
The study is part of a broader University of Maryland research initiative looking at the risk of ischemic stroke in young adults. Ischemic strokes are those caused by a blockage in the brain.
Last month, these Maryland researchers published a study in Stroke: Journal of the American Heart Association that found that risk of stroke among young women increases the more they smoke. Among women under age 50 who smoked 40 or more cigarettes a day, the stroke risk increased more than nine times over that of women who don’t smoke. In 2006, the researchers published a study in Human Molecular Genetics that found a strong association between specific genetic variations and a 50 percent to 100 percent increased risk of stroke in younger women.
Smoking causes the walls of the arteries to thicken and become less elastic, which can lead to plaque and fat accumulation inside the vessels. If the plaque breaks off, it can travel in the bloodstream to the brain, causing a clot and resulting in a stroke. Smoking also makes the blood more “sticky” and likely to clot.
According to Drs. Mitchell and Kittner, a person’s genetic make-up might play a role. “Some people smoke for years and don’t experience these types of problems, while others have a debilitating stroke or develop very significant cardiovascular disease,” Dr. Mitchell says. “Many people who don’t smoke also are at risk for stroke, and our study will look at non-smokers as well.”
“These types of studies will help us better understand the very complex interaction between our genes and our environment. We can’t change our genes, but we might be able to prevent certain medical conditions, such as stroke, by changing our behavior and certain environmental factors,” Dr. Kittner says.
John Cole, M.D.,
an assistant professor of neurology, and Jeff O’Connell, Ph.D., a statistical
geneticist at the University of Maryland School of Medicine, are also co-investigators.
For patient inquiries, call 1-800-492-5538 or click here to make an appointment.