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Researchers Discover new Genetic Variants Associated with Increased Risk of Stroke
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Researchers Discover new Genetic Variants Associated with Increased Risk of Stroke

Researchers Discover new Genetic Variants Associated with Increased Risk of Stroke
News

Researchers Discover new Genetic Variants Associated with Increased Risk of Stroke

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Scientists have identified a previously unknown connection between two genetic variants and an increased risk of stroke, providing strong evidence for the existence of specific genes that help explain the genetic component of stroke.

The research was funded by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health and by several other NIH institutes and centers.

The analysis of over 19,000 participants is published online on April 15, 2009, by the New England Journal of Medicine and will appear in print on April 23, 2009.

The genetic variants were discovered by analyzing the genomes of individuals from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. This extensive resource includes participants from the Framingham Heart Study, Atherosclerosis Risk in Communities study, Cardiovascular Health Study and Rotterdam Study.

"This study, which integrates longstanding observational trials such as Framingham with cutting edge genomic technologies, moves us closer to the era of personalized medicine," said NHLBI Director Elizabeth G. Nabel, M.D. "As we learn more about the role that an individual's unique genetic makeup plays in their overall health, we will ultimately be able to tailor care to better diagnose, prevent, and treat conditions such as stroke."

Stroke is the third leading cause of death in the United States and causes serious long-term disabilities for many Americans.

The research team included Sudha Seshadri, M.D., associate professor of neurology, and Philip A. Wolf, M.D., principal investigator of the Framingham Heart Study and professor of neurology, Boston University School of Medicine, and involved investigators from numerous universities.

Supported by a grant from the National Institute of Neurological Disorders and Stroke (NINDS), Dr. Wolf has studied the risk factors for stroke in the Framingham Heart Study over the past three decades.

The researchers discovered that two previously unsuspected common genetic variants or single-nucleotide polymorphisms (SNPs, pronounced 'snips') were consistently associated with total stroke (all types) and ischemic stroke in white persons.

The SNPs were located on chromosome 12p13 near the gene NINJ2, which encodes ninjurin2, a member of the ninjurin nerve-injury-induced protein family.

"Consistent with the discoveries from genome-wide association studies in many other common disorders, the risk of stroke associated with these SNPs is not sufficiently high to make an individual change their stroke prevention plan. However, the results will lead scientists to direct their attention to new, important biologic mechanisms and hopefully new treatments to prevent stroke," noted Walter Koroshetz, M.D., deputy director of NINDS.

The association of one of the genetic variants was replicated in two independent samples: North American black persons and Dutch white persons. The association held when the analyses were adjusted for systolic blood pressure, hypertension, diabetes, atrial fibrillation, and current smoking.

"This impressive report shows how the power of genome-wide association studies can be enhanced by pooling data from large, population-based studies that follow participants over long periods of time. It also underscores the value of replicating initial results in populations with different demographics," said National Human Genome Research Institute Acting Director Alan E. Guttmacher, M.D.
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