An international team of scientists has identified nearly a dozen genes that contribute to calcium buildup in our coronary arteries that can lead to life-threatening coronary artery disease, a condition responsible for up to one in four deaths in the United States.
Despite the known role of genetics in coronary calcium buildup, only a handful of contributing genes had been identified. Clint L. Miller, PhD, of the University of Virginia School of Medicine’s Center for Public Health Genomics, and his collaborators were eager to identify new genetic factors that influence our risk for coronary calcium buildup.
They did this by analyzing data collected from more than 35,000 people of European and African ancestry around the world. This was the largest such “meta-analysis” yet conducted to understand the genetic basis of coronary artery calcification.
By combining several statistical analysis methods, the scientists identified more than 40 candidate genes at 11 different locations on our chromosomes linked to coronary artery calcification. Eight of these locations had not been previously connected to coronary calcification at all, and five were not yet reported for coronary artery disease. Genes at these locations play important roles in determining the mineral content of our bones and regulate key metabolic pathways in the formation of calcium deposits, among other functions.
One of the genes the scientists identified, ENPP1, is altered in rare forms of arterial calcification in infants. The researchers also identified genes in the adenosine signaling pathway, which is known to suppress arterial calcification.
To validate their findings, the scientists conducted gene queries and experimental studies in human coronary artery tissues and smooth muscle cells and demonstrated direct effects on calcification and related cellular processes.
The researchers have published their findings in the scientific journal Nature Genetics.