April 13, 2018
2 min read

Genetic variant may be effective marker for hypertrophic cardiomyopathy

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A genetic variant has been linked to hyperdynamic features associated with the early stages of hypertrophic cardiomyopathy, according to findings published in JAMA Cardiology.

According to the study, the genetic variant MYBPC325bp occurs in 4% of South Asian descendants, with an estimated 100 million carriers worldwide. Although MYBPC325bp has been linked to cardiomyopathy and HF, the high prevalence the genetic variant implies that other stressors work together with MYBPC325bp.

“Cardiomyopathy features are increased when MYBPC325bp occurs in the presence of other sarcomere gene mutations, explaining some of the variable expression seen with MYBPC325bp,” Shiv Kumar Viswanathan, PhD, a postdoctoral fellow in the division of cardiovascular health and disease at the University of Cincinnati, and colleagues wrote in the study. “South Asian individuals have been the fastest-growing ethnic group in the world during the past decade and defining genetic risk factors in this population has substantial clinical effect. The high prevalence of MYBPC325bp in South Asian individuals exceeds the incidence of cardiomyopathy and heart failure, indicating that MYBPC325bp on its own is not sufficient to cause cardiomyopathy and modifying factors add to its risk.”

The researchers conducted a genotype-phenotype study consisting of 2,401 participants of South Asian descent living in the U.S. who were screened for MYBPC325bp, as well as a subgroup that was clinically evaluated using ECGs and echocardiograms at Loyola University, Chicago, between January 2015 and July 2016.

The genetic screenings showed an MYBPC325bp carrier frequency of 6%, according to the results of the study.

The researchers found a higher frequency of missense TTN variation among MYBPC325bp carriers compared with noncarriers, identifying distinct genetic backgrounds within the MYBPC325bp carrier group.

A total of 9.6% of MYBPC325bp carriers also had a novel MYBPC3 variant, D389V.

Family studies documented D389V was in tandem on the same allele as MYBPC325bp, and D389V was only seen in the presence of MYBPC325bp.

Unlike MYBPC325bp, MYBPC325bp/D389V was associated with hyperdynamic left ventricular performance (mean left ventricular ejection fraction, 66.7%; LV fractional shortening, 36.6%; P<.03) and stem cell-derived cardiomyocytes exhibited cellular hypertrophy with abnormal calcium ion transients.

“What we are seeing is the genetic variant is probably marking a population, and within this group there can be a subpopulation that is even more at risk of cardiomyopathy. We have previously shown that some of the people with no other mutation than just 25-base pair deletion went on to have cardiomyopathy,” Viswanathan said in a press release. “If we can predict in that population those who are at higher risk then we can hone in and focus on them and get them to a physician’s care faster.” by Dave Quaile

Disclosure: Viswanathan reports no relevant financial disclosures. Another author reports she consults for AstraZeneca on matters unrelated to the study.