Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Whole-genome study at Johns Hopkins reveals a new gene associated with abnormal heart rhythm

02.05.2006
Heart rhythm disturbances are target for preventive treatment.

Using a new genomic strategy that has the power to survey the entire human genome and identify genes with common variants that contribute to complex diseases, researchers at Johns Hopkins, together with scientists from Munich, Germany, and the Framingham Heart Study, U.S.A., have identified a gene that may predispose some people to abnormal heart rhythms that lead to sudden cardiac death, a condition affecting more than 300 thousand Americans each year.

The gene called NOS1AP, not previously flagged by or suspected from more traditional gene-hunting approaches, appears to influence significantly one particular risk factor - the so-called QT interval length - for sudden cardiac death. The work will be published online at Nature Genetics on April 30.

"In addition to finding a genetic variant that could be of clinical value for sudden cardiac death, this study also demonstrates how valuable large-scale genomics studies can be in detecting novel biological targets," says the study’s senior author, Aravinda Chakravarti, Ph.D., director of the McKusick-Nathans Institute for Genetic Medicine at Hopkins. "This study, conducted during the early days of a new technology, would have been impossible without the pioneering support of the D.W. Reynolds Foundation in their generous support of our clinical program in sudden cardiac death here at Hopkins."

QT interval measures the period of time it takes the heart to recover from the ventricular beat - when the two bottom chambers of the heart pump. Corresponding to the "lub" part of the "lub-dub" pattern of the heartbeat, an individual’s QT interval remains constant. This interval is partly dependent on one’s genetic constitution and, moreover, genes also play a role in sudden cardiac death.

"There’s a great deal of evidence out there that having a too long or too short QT interval is a risk factor for sudden cardiac death," says the study’s co-first author, Dan Arking, Ph.D., an instructor in the McKusick-Nathans Institute. "This makes it appealing to study because it can be measured non-invasively with an EKG, and each person’s QT interval, in the absence of a major cardiovascular event, is stable over time, making it a reliable measure."

Identifying those at high risk for sudden cardiac death before fatalities occur has been challenging, both at the clinical and at the genetic level, says the study’s other first author, Arne Pfeufer, M.D., of the Institute of Human Genetics at the Technical University in Munich, Germany. Doctors estimate that in more than one third of all cases, sudden cardiac death is the first hint of heart disease. It is widely believed that many factors, genetic and environmental, contribute to irregular heartbeat and other conditions that may lead to sudden cardiac death. Being able to identify predisposed individuals can save their lives by prescribing beta-blockers and other drugs that regulate heart rhythm, and even by implanting automatic defibrillators in those with the highest risk.

In an effort to identify risk factors with a genetic foundation, the researchers took the unconventional approach of starting from scratch and not looking at genes already known or suspected to be involved in heart rhythm.

"Studying individual genes is not going to open new areas of research," says Chakravarti. "Using a whole-genome approach allows us to find new targets that we never would have imagined."

So instead of focusing on so-called candidate genes with known functions that are highly suspect in heart beat rhythm, the team first focused on people who have extremely long or short QT intervals. The researchers used subjects from two population-based studies, about 1800 American adults of European ancestry from the Framingham Heart Study of Framingham, Mass., and about 6,700 German adults from the KORA-gen study of Augsburg, Germany.

The research team then searched for any specific DNA sequences that showed up more frequently in people who have longer or shorter QT intervals than in those with normal QT intervals. To do this, they examined the DNA sequences of both long and short QT people. The human genome contains 3 billion letters, known as nucleotides. Each person’s genome differs from the next person’s by as many as 10 million nucleotides. The researchers looked for single nucleotide variations - known as single nucleotide polymorphisms, or SNPs for short - that track with having a long or short QT interval.

Only one particular SNP correlated with QT interval. That SNP was found near the NOS1AP gene, which has been studied for its function in nerve cells and was not previously suspected to play a role in heart function. However, the research team found that the NOS1AP gene is turned on in the left ventricle of the human heart. And the "lub" part of the "lub-dub" heartbeat corresponds to ventricular contraction. So NOS1AP is active in the right place and time to play a role in QT interval.

Further studies revealed that approximately 60 percent of people of European descent may carry at least one copy of this SNP in the NOS1AP gene. According to the researchers, this particular SNP is responsible for up to 1.5 percent of the difference in QT interval, meaning that other genes, missed in this study, certainly contribute to QT length.

Now that researchers know that variants of the NOS1AP gene correlate with QT interval length, they hope to figure out exactly how the DNA sequence variations alter the function of the gene, and how changes in gene function affects heart rhythm.

Audrey Huang | EurekAlert!
Further information:
http://www.jhmi.edu
http://www.nature.com/ng/index.html
http://www.hopkinsmedicine.org/geneticmedicine/index.html

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>