Study identifies gene variants associated with heart attacks in younger females

A recent study conducted by Massachusetts General Hospital (MGH) discovered mutations in genes involved in the production of fibrillar collagen, the protein responsible for the shaping and strengthening of blood vessels, may lead to spontaneous coronary artery dissection (SCAD).

The study, published in JAMA Cardiology, set out to understand the biological risk factors associated with SCAD, a condition that can lead to fatal heart attacks in women under 50 due to causes that are largely unknown. To do so, a team of MGH researchers examined the genomes of 130 men and women with SCAD and 46,468 people without the syndrome. Using whole-exome sequencing, scientists studied the area of each participant’s genome involved in protein production and regulation.

Results showed rare disruptive variants in 10 collagen genes in all patients with SCAD. In addition, scientists found that those with the condition were 1.75 times more likely to carry rare genetic variants in fibrillar collagen genes than healthy participants. When the two most common genetic variants, Col3a1 and Col5a1, were evaluated in mice, the mice demonstrated an increased risk for arterial dissection and specifically in female mice, arterial diameters were increased, altering the collagen fibril structure.

“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,” study author, Mark Lindsay, MD, PhD, of MGH said in a statement.

This study offers insights into the causes of SCAD and identifies potential genetic variants implicated in it, paving the way for advancements in testing and treatments for the condition.