A research team led by the University College of London (UCL), in the United Kingdom, has identified a new gene as a cause of hypertrophic cardiomyopathy, an inherited heart disease that affects one in every 500 people.
The discovery, published in the European Heart Journal, provides a new causal explanation for 1-2 percent of adults with this disease.
As a result of study, new causal variants, known as ALPK3 (alpha protein kinase) truncating variants, should be added to genetic / screening tests, allowing clinicians to identify more people at risk of developing the disease and who therefore, they would benefit from regular monitoring.
In hypertrophic cardiomyopathy, the heart muscles are thicker, which can make it difficult to receive and pump blood. Although in most cases the condition does not affect daily life, it can cause heart failure and is often cited as most common cause of sudden unexpected death in young people.
About half of the cases already have known genetic causes, linked to between eight and ten specific genes (only two of these unique genes were found in the last decade).
Thus, the main author, Dr. Luis Lopes, from the Institute of Cardiovascular Sciences of the UCL, also a consultant cardiologist of the Barts Health NHS Trust, has pointed out that hypertrophic cardiomyopathy is an “extremely common” genetic condition.
“Previous small-scale studies suggested that variants of the ALPK3 gene could be the cause of a rare pediatric form of cardiomyopathy, but only when two abnormal copies were inherited. We have now shown that a single abnormal copy is enough to cause hypertrophic cardiomyopathy in adults, analyzing a large number of patients and families, “he explained. In this sense, he adds that this form of inheritance (autosomal dominant) is much more frequent, since inheriting a single abnormal copy of a gene is more likely than inheriting two.
“Identifying a new genetic cause is important as it opens up new potential treatment possibilities. It also helps families who have been affected by the disease, but did not know why, namely that one has been found. cause for your specific case“, says the expert.
In the new study, an international team of researchers analyzed the genomes of 2,817 people with hypertrophic cardiomyopathy referred from centers in Spain, the United Kingdom, Denmark, Russia, Latvia, Brazil and Argentina. They compared the prevalence of variant ALPK3 with that of the general population and found that it was 16 times more common.
The researchers also studied the presence of the variant within the families, checking whether or not it was causal by observing if the variant was related to the disease, that is, if the family members who had the variant also suffered from the disease.
The research team examined the different nature of the disease compared to that caused by failures in the sarcomere genes, the main way to inherit the disease. They found that, in cases where the new gene is involved, the disease was diagnosed later (a an average age of 56 years), but had rates of heart failure and heart transplantation similar to those of cases linked to sarcomere genes.
Although little is known about the functional consequences of ALPK3 variants, believed to play a role in regulating protein function through a phosphorylation process. Proteins are essential in the process of contraction and relaxation of heart muscle cells.
In this regard, Dr. Lopes has pointed out that the ALPK3 variants represent a different pathway of the disease than the other main known causes in the sarcomere genes. “This discovery is exciting as it will establish new targets for therapies. Now we have to explore the mechanisms that explain the relationship between ALPK3 variants and disease“, he emphasizes.
In the UK they are offered genetic testing of all those diagnosed of hypertrophic cardiomyopathy in referral centers such as the Barts Heart Center and, if there is a known genetic cause, also in family members.
Although at the moment there is no cure, people who suffer from the disease are monitored regularly, medicated and an important intervention is the implantable cardioverter defibrillator placement (ICD), a device similar to a pacemaker that can deliver a strong electrical shock to the heart if it detects a dangerous abnormal beat.
Eddie is an Australian news reporter with over 9 years in the industry and has published on Forbes and tech crunch.