Mutations protect against heart attack
An international team of researchers led by Professor Heribert Schunkert from the Technical University of Munich has identified genetic variants that significantly reduce the risk of myocardial infarction. This finding may form the basis of new drugs for the prevention of myocardial infarction by simulating the effect of such mutations.
As part of their work, the authors analyzed 13,000 different genes in the genomes of 200,000 participants, some of whom had suffered a myocardial infarction, and the rest acted as a control group. The aim of the work was to find correlations between genetic variants and the risk of coronary heart disease.
Such correlations were found for several genes, including the ANGPTL4 gene encoding angiopoietin-like protein-4. It turned out that mutations inactivating this gene reduce the risk of myocardial infarction by 50%. In addition, it was found that people with ANGPTL4 gene mutations are characterized by significantly reduced levels of triglycerides in the blood.
According to Professor Schunckert, until now the importance of triglycerides in human blood has been greatly underestimated. As a rule, more attention is paid to cholesterol levels. In this case, the so–called "good" cholesterol, or high-density lipoproteins (HDL) and "bad" cholesterol - low-density lipoproteins (LDL) are usually considered separately. At the same time, it is known that the concentration of high-density lipoproteins is always inversely proportional to the content of triglycerides in the blood, and high-density lipoproteins themselves behave neutrally.
Triglycerides, on the other hand, are the second most important class of blood lipids, following immediately after low-density lipoproteins. The only reason why the level of high-density lipoproteins in the blood is still measured is that in combination with the level of triglycerides, this indicator allows you to estimate the concentration of low-density lipoproteins, which cannot be measured by direct methods.
The results of the authors' latest work indicate that the concentration of triglycerides in the blood is influenced not only by the nature of nutrition and hereditary predisposition, but also by the activity of the ANGPTL4 gene. Usually, the protein product of this gene suppresses the functioning of the lipoprotein lipase enzyme, which breaks down triglycerides contained in the blood, which leads to an increase in the level of lipids in the blood. The mutations identified by the researchers disrupt the functionality of this gene, which ensures the maintenance of a low triglyceride content in the blood.
According to the authors, the data they obtained indicate that the body does not need the ANGPTL4 gene at all, and its blocking or inhibition of lipoprotein lipase using other methods may eventually provide protection against coronary heart disease.
Professor Schunckert states that now an important task is to develop drugs that neutralize the effects of the ANGPTL4 gene, thereby reducing the risk of myocardial infarction. He notes that another group of researchers has already achieved this in animal experiments. They managed to significantly reduce the lipid content in the blood of monkeys with the help of neutralizing antibodies against the ANGPTL4 gene. This gives hope that such drugs can be successfully used in clinical practice.
Article by N. Stitziel et al. Coding Variation in ANGPTL4, LPL, and SVEP1 and Risk of Coronary Disease is published in the New England Journal of Medicine.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Technical University of Munich: Mutated gene safeguards against heart attacks.
10.03.2015