Rare gene flaws may shield against heart disease

Four rare mutations in a single gene may reduce the risk of heart disease by 40 per cent, a new study has found.
By scouring the DNA of thousands of patients, researchers at the Broad Institute, Massachusetts General Hospital, and their colleagues discovered the gene mutations that not only lower the levels of triglycerides, a type of fat in the blood, but also significantly reduce a person's risk of coronary heart disease.
The four rare mutations all cripple the same gene, called APOC3, suggesting a powerful strategy in developing new drugs against heart disease, researchers said.
The work sheds light on the biological role of triglycerides and contributes to a growing body of knowledge that suggests that high triglyceride levels - rather than low HDL - are a major culprit in heart disease.

Coronary artery disease, the most common form of heart disease, is a major cause of death worldwide.
Researchers set out to assess the role of rare genetic variants through DNA sequencing. Their goal was to pinpoint specific genes that affect both triglyceride levels and disease risk.

The researchers sequenced the exomes of nearly 4,000 people, searching for genetic variants associated with blood triglyceride levels.
They discovered four distinct mutations, all within the gene APOC3, that are tied to lower blood triglycerides. Remarkably, individuals carrying a single APOC3 mutation had almost 40 per cent lower blood triglyceride levels.
The APOC3 protein is mainly made in the liver and pours out into the blood stream. There, it is thought to prevent the removal of triglyceride-rich lipoproteins from the blood in a few distinct ways, particularly by delaying their clearance following a meal.

The researchers then analysed over 110,000 patient samples and read out, or "genotyped" the relevant parts of the APOC3 gene, and compared heart attack rates in those carrying mutations to those without them.
In the carriers, they found a 40 per cent lower risk of coronary heart disease, suggesting inhibition of APOC3 as a new potential strategy for therapeutic development.
The study was published in the New England Journal of Medicine.