Genetic Mutation May Reduce Coronary Heart Disease Risk

(HealthDay News) — Mutations that affect a single gene may significantly reduce the risk for coronary heart disease (CHD), a new study published in the New England Journal of Medicine suggests.

Researchers found that people with rare mutations that switch off a single copy of the gene NPC1L1 are protected against high levels of LDL cholesterol and CHD.

People with one inactive copy of the gene had a 50% reduced risk for myocardial infarction (MI), according to the study. 

The researchers analyzed data from 113,094 people and found that only 82 had mutations that switched off one copy of NPC1L1. No one had two inactive copies of the gene. 

The researchers estimated that about one in 650 people have an inactive version of NPC1L1. The researchers also noted that NPC1L1 is targeted by ezetimibe (Zetia, Merck).

“This analysis demonstrates that human genetics can guide us in terms of thinking about appropriate genes to target for clinical therapy,” study first author Nathan Stitziel, MD, PhD, a cardiologist at the Washington University School of Medicine in St. Louis, said in a university news release.

“It’s not possible to draw a direct conclusion about ezetimibe from this study,” Stitziel said. “But we can say this genetic analysis gives us some confidence that targeting this gene should reduce the risk of heart attack. Whether ezetimibe specifically is the best way to target NPC1L1 remains an open question.”


  1. The Myocardial Infarction Genetics Consortium Investigators. N Engl J Med. 2014;doi:10.1056/NEJMoa1405386.