Rare gene mutation may slash heart disease risk by 50pc

A new study has revealed that rare mutations that shut down a single gene lower cholesterol levels and helps to reduce the risk of heart disease by 50 percent.

The study conducted by Washington University School of Medicine in St. Louis, the Broad Institute at Massachusetts Institute of Technology and Harvard, and other institutions suggested that the gene, called NPC1L1, is of interest because it is the target of the drug ezetimibe, often prescribed to lower cholesterol.

First author Nathan O. Stitziel, MD, PhD, a cardiologist at Washington University School of Medicine, said that this analysis demonstrated that human genetics could guide them in terms of thinking about appropriate genes to target for clinical therapy and when people had one copy of a gene not working, it was a little like taking a drug their entire lives that is inhibiting this gene.

Researchers analyzed multiple existing studies, pooling data from about 113,000 people.

The investigators found that people with only one working copy of the gene had LDL cholesterol levels an average of 12 milligrams per deciliter lower than the wider population of people with two working copies of the gene. This approximately 10 percent reduction in LDL cholesterol is comparable to that seen in patients taking ezetimibe. But beyond simply lowering cholesterol, the 82 people with inactive copies also had about half the risk of coronary heart disease as people with two functional copies of the gene.

Senior author Sekar Kathiresan, MD, of the Broad Institute, and director of preventive cardiology at Massachusetts General Hospital, said that the protective mutations like the one they had just identified for heart disease were a treasure trove for understanding human biology.

The study is published in The New England Journal of Medicine.