Genetic variants tied to stroke risk

Two common genetic variants that increase the risk of stroke were identified recently by an international research team.

An analysis of data from four genome-wide association studies in the United States and Europe revealed about 20% of whites and 10% of blacks have at least one copy of the variants, and each copy increases the risk of ischemic stroke by approximately 30%.

The study was published online April 15 in The New England Journal of Medicine and slatted to appear in print April 23.

The discovery was made following analyses of the genomes of 19,602 individuals enrolled in four large studies, including the Framingham Heart Study. It then was replicated in two independent samples: blacks from the United States and whites from the Netherlands.

"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 Elizabeth G. Nabel, MD, director of the National Heart, Lung and Blood Institute, which helped fund the research.

Stroke is the third-leading cause of death in the United States and a leading cause of long-term disability, according to the Centers for Disease Control and Prevention. Finding markers that signify heightened risk could allow physicians to treat such people particularly vigorously.

For example, blood pressure and cholesterol levels could be measured earlier and controlled more rigorously and smoking cessation efforts could be stepped up, said author Eric Boerwinkle, PhD, professor of molecular medicine and public health at the University of Texas Health Science Center in Houston.

But that objective has not yet been reached. "We need to develop a stroke risk score," said Boerwinkle, adding that the new research is a first step toward that goal.

"This research gives us a pointer or a beacon on the genome where we can look further," said author Myriam Fornage, PhD, the Laurence & Johanna Favrot Distinguished Professor in Cardiology at the University of Texas Health Science Center.

These findings alone aren't enough to pinpoint who is most at risk, the researchers note. "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, MD, deputy director of the National Institute of Neurological Disorders and Stroke, which also provided funding for the study.

The researchers located the two previously unsuspected common genetic variants or single-nucleotide polymorphisms, also called SNPs, on chromosome 12, near one gene associated with brain injury repair and another connected to blood pressure control.

The genomewide association studies used to locate these variants are a relatively new tool that allows researchers to rapidly scan the complete set of DNA of many individuals to find genetic variations associated with a particular disease or condition.

This technique has revealed numerous relationships between genetic variations and conditions such as type 2 diabetes, obesity and heart disorders.

The researchers are continuing to move ahead on the gene front, Boerwinkle said. "We are doing two things -- looking for additional genes that contribute to stroke risk and using DNA sequence to find the causal mutations within the genes that we already know."

There already are three applications for the information, he added. "It shows that we can identify the genes that are leading to the third-leading cause of death, that we are on our way to a stroke-risk gene score, and that large pharmaceutical companies are very interested in the causes of stroke and may be able to design a better treatment strategy."