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Genetics linked to lower risk of sudden cardiac arrest

Physician-scientists at the Cedars-Sinai Heart Institute have found that a genetic variation is associated with lower risk of sudden cardiac arrest, a disorder that gives little warning and is fatal in about 95 percent of cases. Findings were published by the Public Library of Science (PloS One).

Based on a comparison of the two groups, a genetic variation at the location of the GPC5 gene - a genetic sequence called rs3864180 - was found to be associated with a reduced risk of sudden cardiac arrest.

"If you have this genetic variation in your DNA, it appears that you may have a 15 percent lower likelihood of sudden cardiac arrest," said Sumeet S. Chugh, M.D., associate director of the Cedars-Sinai Heart Institute and one of the senior authors of the study.

The discovery came from a genome-wide association study, which examines the entire set of human genes to detect possible links between genetic variations and specific conditions or diseases. In this study, the Cedars-Sinai Heart Institute researchers compared the genetic makeup of 424 subjects who had experienced sudden cardiac arrest to the DNA of 226 control subjects who had no history of the disorder. All patients had a history of coronary artery disease, which commonly underlies sudden cardiac arrest.

"This kind of genetic analysis is not aimed at identifying a single big gene defect or mutation," Dr. Chugh said. "The goal is to identify a series of smaller novel gene defects that, when grouped together, collectively result in either a protective effect or an increased susceptibility to sudden cardiac arrest."

The authors note that while the protective variant rs3864180 occurs within the GPC5 gene, their results do not definitively prove that the gene itself is involved in sudden cardiac death risk. It is possible, for example, that rs386410 modifies the actions of a different gene or is in proximity to another gene of interest.

Genome-wide association studies are intended to identify regions of the human genome that are associated with development of specific diseases. The GPC5 gene encodes glypican 5, one of the six members of the heparan sulfate proteoglycan (HSPG) family. In the cardiovascular system, cell surfaces and surrounding supportive material express large amounts of these proteins, which are involved in a wide variety of critical cell functions. Additional study of rs3864180 and other variations of the GPC5 gene may lead to a better understanding of the mechanisms leading to sudden cardiac arrest.