Identifying genes that put your heart at risk

Alice McCarthy, February 17th, 2011
  • High cholesterol can lead to blocked arteries, like the one shown here
    (top center), a risk factor for heart attack.
    Image courtesy of National Heart, Lung and Blood Institute

About every 25 seconds, someone in the U.S. will have a heart attack or stroke. Half will die as a result, or approximately 620,000 people every year. This means that heart disease accounts for about 25% of American deaths.

Because heart disease poses such a significant health threat, finding ways to predict who is likely to have a heart attack or stroke remains the subject of intense research.

Even though February is the month formally acknowledged as American Heart Month, it is a disease that is on the minds of many researchers at the Broad every day.

Just this past year, Broad scientists and collaborators published several studies homing in on the genes that influence blood lipid levels, including low-density lipoprotein cholesterol (LDL or “bad” cholesterol), high-density lipoprotein cholesterol (HDL or “good” cholesterol), and triglycerides. Lipid levels are key markers of increased risks of heart attack.

In August, Broad researchers reported in the journal Nature on a genome-wide association study (GWAS) involving more than 100,000 individuals that helped identify 95 gene regions linked to blood lipid levels. Fifty-nine of these regions were identified for the first time as having a role in lipid metabolism, and 13 of them are strongly linked with increased risk of coronary artery disease. Researchers followed up on one of these 95 gene regions, showing a direct role in how it influences lipid levels.

In October, Broad scientists reported on a different approach to finding genes underlying blood lipid levels – studying a single family whose members have a rare disease that causes extremely low LDL levels. The findings were published in the New England Journal of Medicine and discussed in a Broad news story. They identified the gene, possibly a new therapeutic drug target, and expanded the database of information available regarding the link between genes and lipid regulation. Though this particular study relates to a very rare disease associated with extremely low LDL levels, it shines a light on genes associated with LDL metabolism, and could eventually be leveraged to help the estimated 71 million Americans with high LDL levels.

Broad associated reserachers are now working with members of the Broad's Novel Therapeutics Platform to screen for small molecules that interact with several of the new lipid-associated genes in ways that could be of potential therapeutic benefit. This represents an attempt to close the circle from the initial discovery of the genes in human populations to developing new therapies that could reduce the incidence of heart disease.