Rare gene protects against heart disease

Scientists have identified a rare gene variant that protects against cardiovascular disease. A research team at the University of Maryland School of Medicine, Maryland, US, found that carriers of an unusual form of a gene called APOC3 had reduced levels of harmful fat particles in their blood and less hardening of their artery walls, both risk factors for heart disease.

Triglycerides are fat particles from unused food calories that circulate in the blood stream. Individuals with high triglyceride blood levels are at greater risk of heart disease. The new study, published in the journal Science, examined genetic material from 809 members of the Old Order Amish community from Pennsylvania, US. It found that around five per cent of this population carry a mutant copy of APOC3, and that these individuals had reduced blood levels of triglycerides. APOC3 codes for a protein called apoc-III that binds to triglycerides and prevents their breakdown so that they remain in the blood stream longer. The researchers found that individuals with one mutant copy of APOC3 produced half the normal amount of apoc-III, and this appeared to allow them to breakdown triglycerides more quickly, removing them from the bloodstream.

In addition, the carriers of the mutant APOC3 gene had less hardening of their coronary artery walls, which is an early sign of blocked arteries that cause heart disease. They also had lower levels of the so-called 'bad' LDL form of cholesterol that remains in the blood stream and is associated with increased risk of heart disease, and higher levels of the 'good' HDL form of cholesterol which is transported to the liver and broken down. Dr Toni Pollin, a lead member of the research team, said: 'our findings suggest that having a lifelong deficiency of apoC-III helps to protect people from developing cardiovascular disease'.

However, the mutant form of APOC3 is likely to be extremely rare in the general population. The Old Order Amish are a largely closed community descended from a small group of European settlers. This makes them useful for genetic studies as they can track their ancestry back for 14 generations and have similar genetic backgrounds. The researchers believe that the mutant APOC3 seen in the Old Order Amish population can be traced back to a single individual from the 18th century. Nonetheless, Dr Pollin believes that: 'the discovery of this mutation may eventually help us to develop new therapies to lower triglycerides and prevent cardiovascular disease'.