Non-coding genetic variant could improve key vascular functions

Atherosclerotic disease, the slow and silent hardening and narrowing of the arteries, is a leading cause of mortality worldwide. It is responsible for more than 15 million deaths each year, including an estimated 610,000 people in the United States.

In the current issue of the Proceedings of the National Academy of Sciences, a team of physicians, geneticists and biologists describes a previously unknown genetic factor that can either raise or reduce the risk of coronary artery disease or ischemic stroke.

The researchers found that a common non-coding sequence of DNA — known as rs17114036 and located on chromosome 1p32.2 — helps regulate gene expression in the cells that line the interior surface of blood vessels, the vascular endothelium.

This sequence of DNA contains a single nucleotide polymorphism (SNP). These are common. There is, on average, one SNP for every 300 nucleotides scattered throughout a person’s DNA. SNPs tend to reside between genes. Most have no known effect, but some play a distinct role. The research team found that rs17114036 plays a significant role in endothelial function and is relevant to human disease incidence.

“This particular polymorphism is a previously unappreciated layer of regulatory control,” said Yun Fang, PhD, an assistant professor of medicine at the University of Chicago and senior author of the study.

The endothelium helps smooth and speed the flow of blood through complex vascular intersections, places where branches or bifurcations disrupt the flow from an artery to two smaller vessels. When the flow is smooth and in one direction, the endothelium is quiescent. When the flow is disturbed, it leads to chronic local inflammation and formation of atherosclerotic lesions that underlie heart attacks and strokes. This study shows that a piece of regulatory DNA regulates gene expression and may reduce disease risk.