A person's unique genetic makeup may mean greater chances of certain harmful conditions, but other times, one's genes can actually be a defense against negative health outcomes. New research from Washington University’s School of Medicine in St. Louis explores how this concept could help develop therapies intended to reduce the risk of heart attack.

The study—which included help from the Massachusetts Institute of Technology, Harvard University and the University of Pennsylvania—was published March 29 in the Journal of the American College of Cardiology.

In the study, the researchers examined levels of ANGPTL3, a rare gene mutation known to play an important role in processing lipoproteins and molecules that transport fat and cholesterol though the bloodstream, in a single family. Members without this gene had much lower levels of cholesterol and triglyceride in their bloodstream.

Three of the three family members, who didn’t have the gene at all, had extremely low blood cholesterol and no evidence of plaque in their arteries. Additionally, one of the patients without the gene who had high blood pressure, a history of type 2 diabetes and tobacco use still didn’t show any signs of atherosclerosis.

"The family members with complete loss of ANGPTL3 have extraordinarily low cholesterol," said Nathan O. Stitziel, MD, PhD, the lead author on the study and an assistant professor of medicine and of genetics, in a statement. "The interesting thing about this family is the individuals with total loss of this gene had siblings with normal copies of the same gene. So we could compare people with differences in the function of this gene who are otherwise closely related genetically and share similar environments. It's an anecdotal study of one family, but we felt it might provide some insight into the effects of blocking ANGPTL3."

To find answers on the gene beyond the single family, the researchers also looked at data from large population studies. One study, which included about 20,000 patients, showed that those with a partial loss of ANGPTL3 had, on average, 11 percent lower cholesterol levels, 12 percent lower LDL cholesterol levels and 17 percent lower triglyceride levels.

This and other data showed a link between partial loss of the gene and a lower risk for coronary artery disease and heart attack, suggesting that a drug that inhibits ANGPTL3 could reduce these adverse cardiac events.

"We need a better understanding of how cholesterol is processed in individuals with complete loss of ANGPTL3 function before we can fully say what effect inhibiting ANGPTL3 is going to have," Stitziel said. "Studies of people with mutations that completely knock out a gene's function are important because they can provide insight into the potential effects—both good and bad—of drugs inhibiting that gene's function."