Switching off a gene may reduce heart attack risk

Berlin: People with a specific mutation in a gene have a 50 per cent lower risk of suffering a heart attack, which if switched off with medications could reduce the risk of coronary disease significantly, scientists say.

"This discovery makes it considerably easier to develop new medications that simulate the effect of this mutation," said Heribert Schunkert from Technical University of Munich (TUM) in Germany. For the study, scientists analysed 13,000 different genes from a pool of 200,000 participants - both heart attack
patients and healthy control persons.

They were on the lookout for correlations between gene mutations and coronary artery disease. For a number of genes, the researchers registered a correlation, including the ANGPTL4 (angiopoietin-like 4) gene.

In addition, subjects with the mutated ANGPTL4 gene had significantly lower triglyceride values in their blood. "The blood fat triglyceride serves as an energy store for the body. However, as with Low Density Lipoprotein (LDL) cholesterol, elevated values lead to an increased risk of cardiovascular disease. Low values, by contrast, lower the risk," said Jeanette Erdmann from University of Lubeck in
Germany.

"For most patients the focus still lies on cholesterol. A differentiation is always made between the healthy High Density Lipoprotein (HDL) and the harmful LDL cholesterol variants," said Schunkert.

"However, in the mean time we know that the HDL values always run inversely proportional to those of the triglycerides and that HDL itself actually tends to behave in a neutral manner," he added.

"The triglycerides, on the other hand, are the second important blood fat, alongside the harmful LDL cholesterol. The only reason HDL blood values are still measured is because, together with HDL and triglyceride values, they can
be used to derive the LDL values, which cannot be measured directly," Schunkert said.

The new study shows that the concentration of triglycerides in the blood are influenced not only by nutrition and predisposition, but also by the ANGPTL4 gene. "At the core of our data is the lipoprotein lipase (LPL) enzyme. It causes the decomposition of triglycerides in the blood," said Erdmann.

Normally, ANGPTL4 hems the LPL enzyme, causing blood fat values to rise. The mutations identified by researchers disable the function of this gene and thereby ensure that the triglyceride value drops significantly.

"At the same time, we discovered that the body does not even need the ANGPTL4 gene and manages wonderfully without it. It seems to be superfluous. Shutting down the gene or inhibiting the LPL enzyme in another manner may ultimately protect against coronary disease," said Erdmann.

"Based on our results, medications now need to be developed that neutralise the effect of the ANGPTL4 gene, thereby reducing the risk of a heart attack," Schuinkert added.