Gene variants linked to heart attacks in younger adults

March 4, 2022

A tear in blood vessels supplying the heart, called spontaneous coronary artery dissection, or SCAD, is a major cause of serious and potentially fatal heart attacks in adults under 50, especially in women, according to a news release from Massachusetts General Hospital (MGH).

Although the cause of SCAD is unknown, risk factors include female sex, recent childbirth, irregular growth of cells in artery walls (fibromuscular dysplasia), history of migraine headaches, depression/anxiety, and the use of hormones in oral contraceptives or infertility treatments.

Now, researchers at MGH have identified a potential genetic underpinning of SCAD: mutations in genes that control the production of fibrillar collagen, the most abundant protein in the extracellular matrix or “scaffolding” that gives shape, strength, and stability to blood vessels.

They describe their findings in a study published in JAMA Cardiology.

“This shows us that the extracellular matrix, the structural part of the blood vessel, is important in this disorder, specifically the collagenous part of that matrix,” says Mark E. Lindsay, MD, PhD, Investigator at MGH specializing in genetic arterial disease.

Although there are currently no therapies that can help generate or restore collagen in blood vessels, the discovery provides a road map for researchers investigating SCAD and could lead to the development of new therapies or strategies for preventing spontaneous artery dissection in at-risk individuals.

Researchers used the genetic technique known as whole-exome sequencing, which looks at the region of the human genome involved in the production and regulation of proteins. They compared the exomes of 130 women and men with SCAD with those of 46,468 people without SCAD.

They identified rare genetic variants in fibrillar collagen genes that together occurred at a 17-fold higher level than a background of 2506 other genes found in coronary arteries.

In addition, they found that individuals with SCAD were more likely to have these so-called “disruptive” (abnormal) rare variants within fibrillar collagen genes compared with those without SCAD.

“Our findings have implications for genetic testing of patients with SCAD and other arterial dissections, suggesting that it may be helpful to add genes for some additional collagen isoforms to current test panels,” Lindsay says.

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