The majority of sudden cardiac deaths, a leading cause of mortality in the United States and Western Europe, occur when someone is suffering a myocardial infarction or a heart attack. In about 25 percent of patients, heart attacks can cause a deadly arrhythmia known as ventricular fibrillation, the most common mechanism of cardiac arrest.

Miller School researchers collaborating with a team in Amsterdam and others from the U.S. and Europe conducted a genome-wide association study that uncovered a previously unsuspected genetic locus of arrhythmia or sudden death. The findings were published online in July in the journal Nature Genetics.

Nanette Hahr Bishopric, M.D., and Robert J. Myerburg, M.D., collaborated with international scientists on an arrhythmia study.

The international research team performed the genetic study on a set of 972 patients from the Netherlands with a first acute myocardial infarction. Half developed ventricular fibrillation, and half did not. By comparing the two groups, the researchers hoped to identify genetic factors underlying susceptibility to ventricular fibrillation during a heart attack.

“The genome-wide association study turned up a susceptibility locus at chromosome 21q21 that clustered very strongly among the patients who went into ventricular fibrillation,” said Robert J. Myerburg, M.D., professor of medicine and physiology at the Miller School and one of the study’s co-investigators. “The findings suggest that we should look further in that area for identifying people who are at risk for cardiac arrest when they are suffering a heart attack.”

Of the eight single-nucleotide polymorphisms (SNPs) identified in the locus, the one most associated with the risk of ventricular fibrillation was rs2824292. More significantly, the closest gene to that SNP is CXADR, which encodes a protein called the Coxsackie-Adenovirus Receptor.

“The Coxsackie-Adenovirus Receptor imports the viruses, and while infection with adenovirus is almost universal, a few people get a cardiomyopathy that can be very dangerous,” explained Nanette Hahr Bishopric, M.D., professor of medicine, director of the Cardiovascular Genetics Laboratory at the Miller School, and another study co-investigator.

“Infection with Coxsackie B virus is more rare but more commonly causes cardiomyopathy. Both Coxsackie B and Adenovirus 2/5-associated cardiomyopathies are also linked to arrhythmias and sudden death. Given that half of all sudden deaths occur as the first manifestation of underlying disease, it is imperative that we understand the genetic and molecular mechanisms.”

The study findings were replicated in an independent case-control set of patients with myocardial infarction and ventricular fibrillation and a group of patients who survived a myocardial infarction.

The study was supported by research grants from the Netherlands Heart Foundation, the Leducq Foundation in France, and the Interuniversity Cardiology Institute of the Netherlands.