Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene mingling increases sudden death risk

14.10.2009
A multi-national research team has discovered that two genetic factors converge to increase the risk of sudden cardiac death.

The investigators – from the United States, Italy and South Africa – report in the journal Circulation that variations in the gene NOS1AP increase the risk of cardiac symptoms and sudden death in patients who have an inherited cardiac disease called congenital long-QT syndrome.

The findings will help in assessing the risk of sudden death – and assigning therapy – in patients with this syndrome, said senior author Alfred George Jr., M.D., director of the Division of Genetic Medicine at Vanderbilt University Medical Center.

Congenital long-QT syndrome affects the electrical activity of the heart ("QT" refers to a time measure on the electrocardiogram – it is longer than normal in patients with the syndrome). Long-QT syndrome makes patients susceptible to potentially fatal disorders of heart rhythm. It is a known cause of sudden death, especially in young adults and children, and has recently been estimated to affect about one in 2,200 individuals.

But not all people who have gene mutations that cause congenital long-QT syndrome have symptoms (fainting, cardiac arrest, sudden death). The big question mark, George said, is how to manage a patient who has a long-QT gene mutation, but doesn't have any symptoms.

"The concern of course is that the first symptom could be sudden death," he said. "And everything needs to be done to try to prevent that.

"But does every mutation carrier need an implantable defibrillator? Pharmacological therapies? Or should they just be watched?"

The variability in symptoms suggests that other factors play a role – either to promote or prevent symptoms.

George and Peter Schwartz, M.D., at the University of Pavia, Italy, have collaborated over the last seven years to search for "genetic modifiers" of long-QT syndrome – genes other than the disease-causing gene that play a role in the disease.

With collaborators in South Africa, they have focused on a family affected by long-QT syndrome. This extended South African family includes 500 characterized members, 205 of which carry the same long-QT-causing mutation. And as expected, not all of the mutation carriers have symptoms of the disease.

The gene NOS1AP (which codes for a "docking" protein for the enzyme nitric oxide synthase) was identified in a genome wide association study as being a determinant of the QT interval in healthy individuals. George, Schwartz and colleagues examined whether different versions (variants) of the NOS1AP gene impacted the symptoms and QT interval in the South African family.

They found that people who had the primary long-QT-causing mutation and one of two common variants of NOS1AP had a higher probability of cardiac arrest and sudden death than primary mutation carriers who didn't have those NOS1AP variants.

"In this case it appears that variants of NOS1AP somehow predispose those individuals to a worse form of the disease," George said.

The investigators also found that the family members who had the NOS1AP variants had the longest QT intervals – in a group of people who all have long QT intervals.

"We're excited that these findings begin to address how to manage patients with long-QT mutations," George said.

"What we're hoping is that NOS1AP genetic testing in mutation carriers who are asymptomatic or minimally symptomatic could tip the balance toward being more aggressive in treating them or perhaps backing off and watching them for a little longer."

George and colleagues will also continue to search for other genetic modifiers, which could add to a "risk equation" to determine the best therapy.

"Individualizing therapy in this disease is really a paradigm for personalized medicine," George said. "What do we need to know to make a treatment decision? Now we're starting to see how understanding the modifiers that hover around a primary gene mutation may influence the probability of symptoms and help guide therapy."

The National Institutes of Health and Telethon-Italy supported the research.

Leigh MacMillan | EurekAlert!
Further information:
http://www.vanderbilt.edu

More articles from Life Sciences:

nachricht Detailed insight into stressed cells
05.12.2019 | Goethe-Universität Frankfurt am Main

nachricht State of 'hibernation' keeps haematopoietic stem cells young - Niches in the bone marrow protect from ageing
05.12.2019 | Universität Ulm

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The coldest reaction

With ultracold chemistry, researchers get a first look at exactly what happens during a chemical reaction

The coldest chemical reaction in the known universe took place in what appears to be a chaotic mess of lasers. The appearance deceives: Deep within that...

Im Focus: How do scars form? Fascia function as a repository of mobile scar tissue

Abnormal scarring is a serious threat resulting in non-healing chronic wounds or fibrosis. Scars form when fibroblasts, a type of cell of connective tissue, reach wounded skin and deposit plugs of extracellular matrix. Until today, the question about the exact anatomical origin of these fibroblasts has not been answered. In order to find potential ways of influencing the scarring process, the team of Dr. Yuval Rinkevich, Group Leader for Regenerative Biology at the Institute of Lung Biology and Disease at Helmholtz Zentrum München, aimed to finally find an answer. As it was already known that all scars derive from a fibroblast lineage expressing the Engrailed-1 gene - a lineage not only present in skin, but also in fascia - the researchers intentionally tried to understand whether or not fascia might be the origin of fibroblasts.

Fibroblasts kit - ready to heal wounds

Im Focus: McMaster researcher warns plastic pollution in Great Lakes growing concern to ecosystem

Research from a leading international expert on the health of the Great Lakes suggests that the growing intensity and scale of pollution from plastics poses serious risks to human health and will continue to have profound consequences on the ecosystem.

In an article published this month in the Journal of Waste Resources and Recycling, Gail Krantzberg, a professor in the Booth School of Engineering Practice...

Im Focus: Machine learning microscope adapts lighting to improve diagnosis

Prototype microscope teaches itself the best illumination settings for diagnosing malaria

Engineers at Duke University have developed a microscope that adapts its lighting angles, colors and patterns while teaching itself the optimal...

Im Focus: Small particles, big effects: How graphene nanoparticles improve the resolution of microscopes

Conventional light microscopes cannot distinguish structures when they are separated by a distance smaller than, roughly, the wavelength of light. Superresolution microscopy, developed since the 1980s, lifts this limitation, using fluorescent moieties. Scientists at the Max Planck Institute for Polymer Research have now discovered that graphene nano-molecules can be used to improve this microscopy technique. These graphene nano-molecules offer a number of substantial advantages over the materials previously used, making superresolution microscopy even more versatile.

Microscopy is an important investigation method, in physics, biology, medicine, and many other sciences. However, it has one disadvantage: its resolution is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The Future of Work

03.12.2019 | Event News

First International Conference on Agrophotovoltaics in August 2020

15.11.2019 | Event News

Laser Symposium on Electromobility in Aachen: trends for the mobility revolution

15.11.2019 | Event News

 
Latest News

Detailed insight into stressed cells

05.12.2019 | Life Sciences

State of 'hibernation' keeps haematopoietic stem cells young - Niches in the bone marrow protect from ageing

05.12.2019 | Life Sciences

First field measurements of laughing gas isotopes

05.12.2019 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>