NHLBI IN THE PRESS
Researchers use gene-editing tool to more accurately predict an individual’s heart disease risk

Researchers have used gene-editing technology to more accurately predict how a specific gene impacts an individual’s risk for heart disease. In the proof-of-principle study, the researchers sequenced the DNA of 54 healthy people with no history of heart disease and looked at the genes associated with hypertrophic cardiomyopathy, a disease characterized by the abnormal thickening of the heart muscle. The disease, which is believed to be inherited, can cause sudden cardiac arrest and death.

In one individual, they identified a gene called MYL3, which researchers suspect may be linked to hypertrophic cardiomyopathy. To find out, the researchers collected blood samples from the participant and transformed the blood cells into induced pluripotent stem cells—adult cells that can be transformed into virtually any cell type. The researchers then used CRISPR, a gene-editing tool, to modify the stem cells so that they contain the MYL3 variant and subsequently turned the modified stem cells into heart muscle cells. After detailed analysis, they found that the genetic variant was not harmful to the heart cells. 

The researchers believe that similar gene-editing techniques combined with stem cell technologies will allow researchers to predict the fate of other genetic variants on disease processes, particularly if the role of that variant in the disease process is unclear. In so doing, the new approach could speed up the long-awaited era of precision medicine by allowing correction of unwanted mutations, the scientists say. Their study, partly funded by NHLBI, appeared in Circulation, a journal of the American Heart Association.

The researchers also used the gene-editing technique to determine whether a different genetic variant caused an increased risk for a heart-rhythm condition called long QT syndrome, which can cause erratic heartbeats, fainting, and sudden death. The results showed that the variant appeared to play a significant role in the development of the syndrome. That research, which was partly funded by NHLBI, appeared in the Journal of the American College of Cardiology.