A discovery linking mutations in a single gene to lower cholesterol and a reduced risk of heart disease offers new directions for treatment drugs.

Rare mutations in a single gene are linked to lower cholesterol levels and can cut the risk of heart disease by half, research has shown.

Scientists believe the discovery might guide the way to new treatments.

The gene, known as NPC1L1, is already the target of one cholesterol-lowering drug, ezetimibe, which works in a different way from more widely prescribed statins.

Researchers found that people with one inactive copy of the gene - which normally works in pairs - seem to be protected against raised low-density lipoprotein (LDL), the harmful form of cholesterol that damages arteries.

Dr Nathan Stitziel, a member of the team from Washington University School of Medicine in the US, said: "This analysis demonstrates that human genetics can guide us in terms of thinking about appropriate genes to target for clinical therapy.

"When people have one copy of a gene not working, it's a little like taking a drug their entire lives that is inhibiting this gene."

The study involved pooling together DNA study data from around 113,000 people. Of these, only 82 possessed a mutation that shut off one copy of the NPC1L1 gene. None of the participants had two inactive copies.

Roughly one in 650 individuals carry an inactive version of the gene, the scientists estimated.

The research, published in The New England Journal of Medicine, showed that people with just one working copy of the gene had LDL cholesterol levels 12 milligrams per decilitre lower on average than the average population.

This equated to a reduction of about 10 per cent - roughly the same level achieved by taking ezetimibe.

But those with inactive copies of NPC1L1 also had about half the risk of coronary heart disease as people with two functional copies.

Senior author Dr Sekar Kathiresan, director of preventive cardiology at Massachusetts General Hospital, said: "Protective mutations like the one we've just identified for heart disease are a treasure trove for understanding human biology. They can teach us about the underlying causes of disease and point to important drug targets."

Statins stop the body manufacturing its own cholesterol. In contrast, ezetimibe blocks absorption of cholesterol in the gut by inhibiting the protein made by NPC1L1.

While the drug is known for its cholesterol-lowering effect, the jury is out on whether it also reduces the risk of heart disease.

"It's not possible to draw a direct conclusion about ezetimibe from this study," said Dr Stitziel. "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."


Copyright AAP 2014