Multiple Rare Gene Mutations Associated With Increased Risk of Heart Attack

Research performed at Washington University and other leading biomedical research institutions found that multiple rare mutations in two genes increase an individual’s risk of heart attack. The research appears online this week in the journal Nature.

Nathan Stitziel, MD, PhD, a cardiologist at Washington University School of Medicine and co-first author of the report, helped to lead the analysis team. The study involved sequencing the entire protein-coding portion of the genome-also called the exome-in approximately 10,000 individuals, half of whom had heart attack at an early age and half who had not had any heart attack. After the research team examined the exomes to detect significant differences between heart attack victims and controls, they found two genes, LDLR and APOA5, in which mutations increase an individual’s risk of disease.

Specifically, they found that multiple rare mutations in LDLR were associated with higher levels of LDL cholesterol and increased risk of heart attack, while multiple rare mutations in APOA5 increased blood triglycerides in addition to raising heart attack risk. “For over 40 years elevated LDL cholesterol has been known as one of the major risk beyond LDL cholesterol,” said Stitziel. “Large genetic studies like this one are an amazing resource for providing insight into the biology of human disease and pointing toward new therapeutic targets.”

The research was published online December 10, 2014 in Nature.