Rare Genetic Mutation Helps Fight Heart Disease

The advent of genetic research and medicine hastened the discovery of a secret arsenal hidden in our genetic code. Some rare genetic mutations have been found to improve human resistance to infections, diseases and even some extreme environments. And what science learns about these mutations contributes to the development of new drugs and gene therapies, as well as preventive medicine.

One such mutation involves the ANGPTL3 gene. This gene is critical in the synthesis of lipoproteins that transport fat and cholesterol through the bloodstream, and a recent study has found that people with low or no expression of the ANGPTL3 gene enjoy lower levels of bad cholesterol and triglycerides. These “mutant people” are, therefore, more protected against cardiovascular disease than others.

Washington University School of Medicine carried out a study of one small family with a few members featuring rare mutations of the ANGPTL3 gene. They compared the findings with an analysis of data from a large-scale study (over 20 thousand participants) to confirm that low or no ANGPTL3 activity results in lower levels of LDL cholesterol and triglycerides. This was reflected in the health of the family members – these people revealed no signs of plaque accumulation in coronary arteries. The most impressive was that one of these individuals was a heavy smoker, had high blood pressure and endured diabetes type 2 (all high risk factors), and yet showed no signs of atherosclerosis.

Overall, the scientists were able to associate low or no ANGPTL3 expression with a lower risk of heart attack and coronary artery disease. This study—published in the Journal of the American College of CardioIogy—shows how the effects of a rare gene mutation can educate scientists about the possible benefits or disadvantages that a ANGPTL3-inhibitor drug could bring to people facing risk of cardiovascular disease. Similarly, these findings can help develop new gene therapy solutions in the future.

There are also two other genetic mutations known to result in abnormal levels of cholesterol (PCSK9) and triglycerides (APOC3). PCSK9-inhibitor drugs have recently shown promising results as a measure to reduce cholesterol levels. And there is substantial evidence suggesting that APOC3 inhibitors could provide a similar benefit. However, the benefit of focusing attention on the ANGPTL3 gene is that its inhibition would affect both cholesterol and triglycerides at the same time. Such a drug seems very promising on paper, but scientists highlight that more research is necessary to fully grasp how cholesterol is managed by people with a mutated ANGPTL3 gene.