Sudden cardiac death: New genetic mutations discovered

Nazarbayev University researchers have discovered new genetic factors associated with heart failure and sudden cardiac death.  Studying these genetic markers will help scientists to better understand heart disease, which could be used in the future to screen individuals for potential risks related to developing heart conditions. The results of this unique genetic research are published in the peer-reviewed scientific journal Plos One.

According to US cardiologists, sudden cardiac death is the cause of every fourth natural death worldwide. Sudden cardiac death is often due to the heart having problems pumping blood (ventricular  fibrillation), or to sudden spikes in pulse with over 150-300 heart beats per minute (paroxysmal ventricular tachycardia of the heart)[1]

Analysis of electrocardiograms from patients who died of sudden cardiac death shows that in 83.5% of cases the deceased had either ventricular arrhythmias or less frequently bradycardia resulting in cardiac asystole.  In about 5 to 12% of cases, sudden cardiac death occurred in previously asymptomatic and seemingly healthy people.  Based on these data, scientists are convinced that ventricular arrhythmias are associated with a high probability of developing fatal arrhythmias or the so-called “sudden arrhythmic death” – where the reason for heart failure is not always apparent.  

“Genetically determined diseases or channelopathies are associated with impaired flow of potassium or calcium ions in the muscle cells of the heart. They are also a major cause of heart failure and sudden cardiac death worldwide,” – says Ainur Akilzhanova, MD, Ph.D., Head of the Laboratory of Genomic and Personalized Medicine at National Laboratory Astana.

How do genetic factors and non-genetic factors such as environment and lifestyle affect the likelihood of developing heart disease?   Might certain genetic mutations predispose people to sudden cardiac death?  NLA genetic scientists attempted to answer these questions in a recent study of mutations of the ryanodine receptor-2 gene (RYR2).  The RYR2 gene is one of the key players tightly regulating calcium ions (Ca2 +) efflux from the sarcoplasmic reticulum (a part of cardiac myocyte where calcium ions are stored) to the cytosol.   Maintaining correct amounts of calcium ions throughout the body is important for heart muscle health and normal heart beating, and people with certain RYR2 mutations might have issues with proper calcium ion regulation.  Mutations in this gene have been linked to an inherited disorder that could result in life-threatening irregular heartbeats called catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1).

In the framework of the project, scientists studied the DNA of 70 Kazakhstanis looking for genetic mutations of the RYR2 gene.  Specifically, they examined the genes of 35 patients who had been diagnosed with different types of ventricular tachycardia and their family members.  Nazarbayev University scientists have discovered two novel and previously unknown genetic variants that can influence the development of ventricular tachycardia. In addition, we identified a known variant previously associated with arrhythmogenic right ventricular dysplasia type2 (ARVD2).

Moreover, researchers evaluated the clinical significance of novel and rare genetic variants in the development of arrhythmias in Kazakhstani patients with diagnosed ventricular tachycardia and their healthy family members. These results will assess the risks of developing cardiac disease and sudden cardiac death in Kazakhstan and help doctors to develop measures for their prevention.

Dr. Akilzhanova noted that using genetic information to help treat CPVT is a fairly new approach that was not widely used until 2000.  In 2001, the role of mutations of the RYR2 gene in the development of CPVT1 was first proved. Heart Rhythm Society and the European Heart Rhythm Association recommend early genetic testing of family members because CPVT may present as SCD or Sudden Infant Death Syndrome as the first manifestation.  Nazarbayev University researchers emphasize that the clinical observation of patients carrying genetic factors will contribute to the understanding of further risk factors and their impact on the development of heart disease.


[1] The human heart consists of four separate chambers – the heart has a right and a left side, with upper (atria) and lower (ventricle) chambers.  All four chambers play an important role in pumping blood.