36 new genes implicated in cardiac disease

Researcher developed a new personalized method to determine genes suspected in complex diseases. The main agenda of this research is to generate illustrated restorative drugs to reverse heart disease.

One in four deaths in the US every year is due to heart disease, according to the Centres for Disease Control and Prevention. It's the leading killer of both men and women, but the disease's genetic complexity makes it difficult to treat.

In a recently-published paper, researchers describe their discovery of 36 previously unknown genes implicated in heart failure. The team confirmed that one of those genes plays a fundamental role in cardiac hypertrophy and abnormal thickening of the heart muscle which may lead to heart failure.

The method can predict beforehand whether a patient should be prescribed a different drug using just a simple blood test. This would save time and accelerate the therapy. In general, this research highlights the importance of personalized approaches to uncover novel disease genes and better understand disease processes.

The traditional approach to finding genes related to heart disease works like this: Researchers take donated hearts from people who died unexpectedly but were previously healthy. They analyse the gene expression i.e., the amount of messenger RNA and proteins produced by the genes of healthy hearts and compare it with the gene expression of sick hearts explanted from end-stage heart failure patients undergoing heart transplant.

Where you see a different gene expression profile. For example, if a gene found in the sick hearts expresses twice the amount of RNA as it did in the healthy hearts, it might be relevant to the disease. But so far, researches said this method hasn't been very successful in finding important genes.

Researchers had taken it in an entirely different approach using the Hybrid Mouse Diversity Panel, a collection of 100 genetically different strains of mice that can be used to analyse the genetic and environmental factors underlying complex traits. Within each strain, the mice are inbred, making them all identical twins on a genetic level.

Researchers took two mice from the same strain and gave one of them a stressor drug that induces heart failure. They then compared the stressed mouse's gene expression with its non-stressed twin. Since the mice have the same genome, they were able to pinpoint individual genes that changed expression as a direct result of the heart stressor. The researchers identified 36 such genes.

Many of these genes were previously unknown to be implicated in heart failure. Researchers said one of them is known as a transcription factor. The researchers confirmed the gene's role by using molecular biology techniques to silence it and observe the resulting changes of expression. They found the transcription factor gene was directly connected to a whole network of proteins known to play a role in cardiac hypertrophy.

One of the genes researchers found, called RFFL, was previously known to researchers to be implicated in other cardiac processes. However, it was not known to be related to hypertrophy.

All of the sudden, this study reveals the gene is important for the hypertrophic trait. We now think that RFFL is important nodes that can cross-talk with cardiac hypertrophy failure and cardiac excitation. Cardiac excitation is the process that enables the chambers of the heart to contract and relax. That was something that we wouldn't have explored, given what we knew about RFFL.

As a next step, researchers said the new method could be tested on human stem cells, which have the same genetic code as the person they came from and can be induced to have similar gene expression patterns as heart cells.

When you are comparing two populations of cells from the same person one that has been controlled and one that has been under the effect of a drug or stressor you can compare the change of gene expression in a personalized way.

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