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A recent study published in the journal Nature Genetics identified 10 new genetic regions associated with Brugada syndrome, a cardiac arrhythmia associated with sudden death in young adults
The findings expand the possibilities for predicting risk scores and provide new targets for therapeutic research, said Alfred George, Jr.
"Prior to this work, there were only two genomic regions associated with Brugada syndrome risk through genome-wide studies
Brugada syndrome (BrS) is an inherited disorder characterized by life-threatening irregular heartbeat
To identify new susceptibility genes, the scientists built a vast database of nearly 3,000 unrelated BrS patients from 12 countries, then performed a genome-wide association analysis and correlated the results with 10,000 Patients without BrS were compared
Many of these regions are located on chromosome 3 and contain genes known to encode two sodium channels, SCN5A and SCN10A
Subsequently, Northwestern University researchers used the CRISPR-Cas9 gene editing technology to knock out an important cardiac microtubule gene mapre2 in human cells and found that the gene is essential for stabilizing the microtubule network in cardiomyocytes, which pass through Contraction to control the beating of the heart
The plethora of genetic associations revealed by this study suggest that BrS has a complex origin, George said
"This study further supports that BrS is not a simple single-gene disorder, but rather a disorder with a complex genetic susceptibility to cardiac arrhythmias," said George
Furthermore, according to the authors, the size of this analysis means that a polygenic risk score for BrS may help quantify sudden cardiac death risk in other arrhythmic conditions
