Researchers who conducted a genome-wide association meta-analysis of eight studies into Spontaneous Coronary Artery Dissection (SCAD), which can lead to heart attacks – particularly in women under 60 – found 16 gene variants linked to an increased risk of the condition.
SCAD can occur suddenly, with no warning and often affects people who are otherwise healthy, making it difficult to detect early, reports Medical News Today.
The team, from the United Kingdom, France, Australia, Canada and US, had collaborated to examine whether there were genetic factors contributing to someone developing SCAD, and to learn more about what causes it.
The study, published in Nature Genetics, identified 16 genes, including those involved in artery integrity and blood clotting, that are associated with an increased risk.
Conducting a meta-analysis
The researchers compared a group of 1 917 people with SCAD to a control group of 9 292: included were patients with SCAD who had similar clinical characteristics and met diagnostic criteria. They then analysed genes that were possibly “regulated in vascular smooth muscle cells”, as well as genes involved in blood coagulation.
This is significant because blood coagulation, or blood clotting, prevents an injured vessel from bleeding profusely. An injured blood vessel can lead to a heart attack in SCAD.
The research team also investigated the causal relationships between cardiovascular disease risk factors (predicted based on genetics) and SCAD and coronary artery disease (CAD).
In their combined genetic analysis of the eight studies, they found 16 genes that factor into SCAD.
They found that lower expression of the tissue factor gene F3, involved in blood coagulation, is associated with a higher risk of SCAD, and a “novel association signal with SCAD” with the gene THSD4 that is associated with fibrillin, which regulates heart functioning.
The team also found causal genes involved in maintaining arterial wall integrity and function, including genes HTRA1, TIMP3, ADAMTSL4, LRP1, COL4A1, and COL4A2.
“This research confirms there are multiple genes involved in determining the risk of a person having a SCAD,” said lead study author Dr David Adlam, associate professor of acute and interventional cardiology at the University of Leicester in England.
The team also found that some of the genetic variants in SCAD and coronary artery disease (CAD) are connected but have an opposite impact.
“Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms,” wrote the authors.
What is SCAD?
SCAD happens when a tear spontaneously occurs within the artery wall and causes blood to get trapped. This narrows or blocks the artery and can cause a heart attack because blood flow can’t reach the heart muscle.
While typical coronary artery disease often affects people with certain risk factors (such as a family history of it or people with high cholesterol levels), SCAD can occur without warning and in people who are healthy.
SCAD mostly affects young women and is the cause of 25% of acute coronary syndrome cases in women under 50. Additionally, SCAD can cause heart attacks in pregnant women.
While symptoms can vary, they may resemble symptoms of a heart attack and may include chest pain, shortness of breath, profuse sweating and dizziness.
Study details
Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation
David Adlam, Takiy-Eddine Berrandou, Nabila Bouatia-Najim et al.
Published in Nature Genetics on 29 May 2023
Abstract
Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritised genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.
MedicalNewsToday article – Scientists find 16 genes that increase risk for heart attacks in women
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