Preventing coronary artery disease through gene discoveries

Genome-wide study uncovers coronary artery calcification insights.

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Scientists worldwide found almost 11 genes linked to calcium buildup in our heart arteries, which can cause deadly heart disease. This condition is responsible for one in four deaths in the United States. These genes could be treated with existing medicines or supplements to slow down or stop the disease from worsening.

Dr. Clint L. Miller, a researcher from the University of Virginia School of Medicine, said, “By sharing important genetic and health information gathered over many years, our team discovered new genes that might predict heart disease. This is a crucial first step in finding the biological reasons to prevent heart disease.

Before people show signs of heart disease, doctors can use CT scans to find calcium buildup in their heart arteries. This helps predict future heart problems like heart attacks or strokes, which are common causes of death worldwide. Calcium buildup is also linked to other age-related diseases like dementia, cancer, kidney problems, and hip fractures.

While we knew genetics played a role in calcium buildup, we didn’t know many genes involved. So, a team led by Dr. Miller collected data from over 35,000 people from different backgrounds worldwide. This is the most extensive study aiming to determine which genes affect calcium buildup in heart arteries.

Miller said, “Coronary artery calcification reflects the vessel’s lifetime exposure to risk factors. While previous studies from over a decade ago identified a handful of genes, it was clear that larger and more diverse studies would be necessary to identify the pathways underlying coronary artery calcification.”

Using multiple statistical analysis methods, scientists found more than 40 genes connected to calcium buildup in the heart arteries at 11 different spots on our chromosomes. Eight sites were not previously linked to this condition, and five were never associated with heart artery disease. These genes are essential for our bone mineral content and play a role in forming calcium deposits and other vital processes.

One gene they found, ENPP1, is linked to rare types of calcium buildup in infants’ arteries. The researchers also discovered genes in the adenosine signaling pathway, which helps prevent artery calcification.

The scientists performed gene tests and experiments on human heart artery tissues and muscle cells to confirm their findings. These experiments showed that the genes directly impact the calcium buildup and related processes.

Now that these genes’ roles in heart artery calcification are known, scientists can try to create new medicines or find existing ones that can target these genes or the proteins they produce to control the calcification process. Diet changes or supplements like Vitamin C or D might influence some of these targets.

Although more research is needed to understand the best way to target these genes and processes, Dr. Miller believes these discoveries could lead to better risk assessment and early treatments to stop heart disease from worsening. This could be a significant breakthrough in fighting a condition that causes more than 17 million deaths yearly worldwide.

Miller, of UVA’s Departments of Biochemistry and Molecular Genetics and Public Health Sciences, said, “This interdisciplinary collaboration reveals the power of meta-analyses for an understudied and clinically relevant measurement. We look forward to continued progress in translating these preliminary findings to the clinic and identifying additional genes that could generalize risk prediction across more diverse populations.”

In conclusion, identifying critical genes associated with coronary artery disease and calcium buildup in heart arteries is promising for future prevention and treatment strategies. By understanding these genetic factors, researchers can explore the development of drugs, dietary interventions, and targeted therapies to reduce the risk and progression of coronary artery disease. These discoveries offer hope for a significant impact on a condition responsible for millions of annual deaths worldwide.

Journal Reference:

  1. Kavousi, M., Bos, M.M., Barnes, H.J. et al. Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification. Nature Genetics. DOI: 10.1038/s41588-023-01518-4.
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