Scientists studying genetic data from nearly 50,000 people have uncovered several DNA sequence variations associated with the electrical impulses that make the heart beat. The findings, reported in Nature Genetics, may pave the way for a greater understanding of the mechanisms for abnormal heart rhythms and sudden cardiac death.
"Regulation of the heart's rhythm is exceedingly complex," says co-author Glenn I. Fishman, MD, the William Goldring Professor of Medicine and the director of the Leon H. Charney Division of Cardiology at NYU Langone Medical Center. "This study provides new clues about the biologic pathways that influence cardiac conduction. Our hope is that this information will translate into novel approaches to prevent or treat serious rhythm disorders, including sudden cardiac death."
Normally, signals start from specialized muscle cells called pacemaker cells, travel through the heart and cause rhythmical muscle contractions – a system called cardiac conduction. The signals register on heart monitors as the electrocardiogram, or ECG. Abnormalities in cardiac conduction, particularly in the ventricles of the heart, can be extremely dangerous, leading to sudden cardiac death which affects approximately 250,000 people each year in the United States. Treatment with a pacemaker or a specialized device known as an implantable defibrillator may be needed to regulate the heart's rhythm.
Researchers have known for some time that genetic factors contribute to electrical activity in the heart, including conduction of the electrical signal throughout the heart chambers. The new study reports on several previously unsuspected regions in the genome associated with cardiac electrical activity.
An international collaboration of scientists identified genetic associations with cardiac ventricular conduction in 22 regions of the genome in the largest study of its kind in conduction. The data was generated by an analysis of 15 European and American centers, representing nearly 50,000 individuals of European descent. Genome-wide association studies examine hundreds of thousands of genetic variants in thousands of people to try to find sequence variants and genes associated with particular diseases or conditions.
Some of these genetic variations were found in two sodium channel genes that sit side-by-side on the human genome. Sodium channels are molecular gated pores in living cells that control the flow of sodium ions – electrically charged particles – critical for the heart beat. The first gene, SCN5A, is well known to be involved in cardiac conduction. The second, SCN10A, has only recently been found in the heart.
As part of the study, Dr. Fishman and his team at NYU Langone identified where in the heart the SCN10A channels reside and discovered they were particularly abundant in specialized conduction fibers of the mouse heart key to the orderly contraction of the heart. The researchers then treated mice with a drug that selectively blocked this sodium channel and found that cardiac conduction was delayed, affecting the ECG. In addition to cardiac sodium channel genes, the study found that a number of other genes and genetic pathways involved in cardiac conduction, including calcium handling processes and transcription factors which influence cardiac development and formation. Dysfunctions in these processes before birth can lead to heart malformations in newborns.
Lead and corresponding author of the study is Dr. Nona Sotoodehnia from the University of Washington. Dr. Stefan Kaab of Ludwig-Maximilians-University in Munich, Germany, and Dr. Dan E. Arking at Johns Hopkins University in Baltimore are also corresponding authors. More than 100 scientists from the United Kingdom, Europe and the United States contributed to the work. The study was funded in part by the National Institutes of Health in Bethesda, Maryland.
ABOUT NYU LANGONE MEDICAL CENTER
NYU Langone Medical Center, a world-class patient-centered integrated academic medical center, is one of the nation's premier centers for excellence in health care, biomedical research, and medical education. Located in the heart of Manhattan, NYU Langone is comprised of three hospitals—Tisch Hospital, a 705-bed acute-care tertiary facility, Rusk Institute of Rehabilitation Medicine, the first rehabilitation hospital in the world, with 174 beds and extensive outpatient rehabilitation programs, and the 190-bed Hospital for Joint Diseases, one of only five hospitals in the world dedicated to orthopaedics and rheumatology—plus the NYU School of Medicine, one of the nation's preeminent academic institutions. For more information, visit http://www.med.nyu.edu/.
Dorie Klissas | EurekAlert!
Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel
Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
24.05.2017 | Physics and Astronomy
24.05.2017 | Physics and Astronomy
24.05.2017 | Event News