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

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.


'"/>

Source:Johns Hopkins Medical Institutions


Related biology news :

1. Bioartificial kidney under study at MCG
2. W.M. Keck Foundation funds study of friendly microbes
3. Yellowstone microbes fueled by hydrogen, according to U. of Colorado study
4. Genome-wide mouse study yields link to human leukemia
5. Clam embryo study shows pollutant mixture adversely affects nerve cell development
6. New imaging method gives early indication if brain cancer therapy is effective, U-M study shows
7. Same mutation aided evolution in many fish species, Stanford study finds
8. Sequencing of marine bacterium will help study of cell communication
9. Genetically modified rice in China benefits farmers health, study finds
10. A new study examines how shared pathogens affect host populations
11. NYU study reveals how brains immune system fights viral encephalitis
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/2/2016)... Feb. 2, 2016  BioMEMS devices deployed ... focused on medical screening and diagnostic applications, ... Wearable devices that facilitate and assure continuous ... movement are being bolstered through new opportunities ... signal acquisition coupled with wireless connectivity and ...
(Date:2/2/2016)... VIEW, Calif. , Feb. 2, 2016 /PRNewswire/ ... retinopathy market, Frost & Sullivan recognizes US-based Intelligent ... America Frost & Sullivan Award for New Product ... provider in North America , ... in the rapidly growing diabetic retinopathy market. The ...
(Date:1/27/2016)... , Jan. 27, 2016  Rite Track, Inc. a ... West Chester, Ohio announced today ... service staff, based in Austin, Texas ... ability to provide modifications, installations and technical support offerings ... CEO of PLUS, commented, "PLUS has provided world class ...
Breaking Biology News(10 mins):
(Date:2/4/2016)... (PRWEB) , ... February 04, 2016 , ... ... talent development and compliance training, today announced an interactive FDA compliance training ... The RAPS (Regulatory Affairs Professional Society) accredited interactive course on Morf Playbook—now ...
(Date:2/4/2016)... SHENZHEN, China , Feb. 4, 2016 ... government, and various medical institutions attended a ceremony in ... provide integrative, personalized cell therapy in 2016. ... the "Shenzhen Clinical Translation Platform for Personalized Cell Therapy" ... Shenzhen Regional Cell Production Center, both subsidiaries of Beike ...
(Date:2/4/2016)... Feb. 4, 2016  Spherix Incorporated (Nasdaq: SPEX ... and monetization of intellectual property, today provided an update ... the Northern District of Texas ... Inter Partes Re-examination ("IPR") proceedings that ... The IPR was initiated on only certain claims of ...
(Date:2/3/2016)... 2016   ViaCyte, Inc ., a leading, ... stem cell-derived islet replacement therapy for the treatment ... announced that ViaCyte and Janssen Biotech, Inc., one ... Johnson, have agreed to consolidate the assets of ... provides ViaCyte with an exclusive license to all ...
Breaking Biology Technology: