Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists discover two genes linked to early heart attack risk

12.05.2006
Scientists at UCSF, Celera Genomics and The Cleveland Clinic have discovered two gene variants associated with a significantly increased risk for early heart attack, or myocardial infarction (MI).

One of the genes, known as VAMP8, normally expresses a protein essential for early stages of clotting. When clotting occurs in a coronary blood vessel, it can lead to heart attack. Knowing gene mutations that increase heart attack risk can help identify people at risk and clarify molecular changes involved in heart disease. This knowledge can lead to new potential drug targets to treat the disease.

The research will be reported in the July 2006 edition of Arteriosclerosis, Thrombosis, and Vascular Biology and is being made available online May 11, 2006 on the publication’s website at http://atvb.ahajournals.org/.

A person with either of the two gene variants has about twice the risk of early heart attack as someone with neither, the research showed. The retrospective study analyzed clinical records and gene variations in more than 2,000 patients and controls in three independent investigations. All study participants were Caucasian, and the average age of heart attack among the cardiac patients was under 60.

Neither of the two genetic variants, known as single nucleotide polymorphisms or (SNPs), has previously been associated with heart attack. VAMP8 is involved in platelet aggregation. The other gene, HNRPUL1, encodes a protein involved in RNA activity.

Celera Genomics (NYSE:CRA) is an Applera Corporation business.

"This research and other large, carefully controlled studies can provide valuable insights into genetic contributions to early-onset heart attack," said John P. Kane, MD, PhD, professor of medicine at UCSF and associate director of UCSF’s Cardiovascular Research Institute. "A number of studies have identified genes linked to increased heart attack risk, but many of the studies have been made with a single cohort of patients and have not been replicated. The new study involved three sequential cohorts, and applied a statistical analysis that increases the likelihood that these are indeed true associations."

Kane, a collaborator and a co-author on this study, was senior author on a paper published last fall with many of the Celera colleagues, identifying four gene variants associated with heart attacks. Kane and his UCSF colleagues have identified nine genes linked to increased heart attack risk thus far.

He suspects that the newly discovered variant of VAMP8 either speeds the clotting process, triggers it too early or allows clotting to continue too long.

"We are now eager to screen the population for people with two copies of this gene and study its action at the molecular level," Kane said. "VAMP 8 could be a target for a new drug."

Large scale studies like this one, with well-characterized samples from carefully selected patients, hold significant promise to enable the development of new diagnostics and targeted therapeutics, the scientists say.

"In order for genetic marker studies to translate into diagnostic tests with significant medical impact, discovery study results must be reproducible and applicable to a wide group of people," said Tom White, PhD, chief scientific officer at Celera Genomics. "Too often, when new markers are reported, the disease association cannot be confirmed because the study used a small sample set. In addition, a spurious disease association could be found due to chance alone if a large number of SNPs are not tested."

The size of this study and the identification of VAMP8, coupled with other prospective studies of the general population underway at Celera, are providing valuable insight toward the development of a "Genetic Risk Score" that is expected to identify individuals at elevated risk for heart disease, White said.

Celera evaluated DNA samples from more than 2,000 individuals in three studies to compare patterns of genetic variation in people with a history of early-onset MI to those with no history of heart disease. The results were significant in all three studies.

The key finding of the study was that variants of the VAMP 8 and HNRPUL1 genes were associated with early-onset MI, and the same variants were associated with risk in all three studies. Each of these gene variants individually confers an increased risk for MI that is comparable to conventional risk factors such as smoking, high blood pressure and elevated cholesterol levels.

These genetic markers were identified through a genome-wide study of 11,647 single SNPs in 7,136 genes. The study focused on SNPs that could influence gene function in order to increase the likelihood of identifying disease-causing gene variants. These were tested for association with early-onset MI in three case-control studies with a total of 821 cases and 1,200 controls.

Two of the samples drew on the very large and complete collection of clinical records, blood samples, DNA analysis and other records of more than 27,000 heart disease patients stored and studied as part of the Genomics Resource in Arteriosclerosis at UCSF’s Cardiovascular Research Institute (CVRI). The third sample comes from a collection at The Cleveland Clinic

The study is a collaboration of UCSF, Celera, The Cleveland Clinic Foundation, Case Western Reserve University and Brigham Young University.

First author on the paper is Dov Shiffman, PhD, senior staff scientist at Celera. Co-authors at Celera are James J. Devlin, PhD, director of cardiovascular research, and Charles Rowland, Judy Louie, May Luke, Lance Bare , Joel Bolnick, Bradford Young and Joseph Catanese.

Colleagues and co-authors with Kane at UCSF’s CVRI are Mary Malloy, MD, UCSF professor of medicine and pediatrics, and Clive Pullinger, PhD, adjunct associate professor of genetics. Other co-authors on the paper are Stephen Ellis, MD, director of the Sones Cardiac Department of Cardiovascular Medicine and professor of medicine at The Cleveland Clinic, Charles Stiggins at Brigham Young University, and Eric Topol at Case Western Reserve University.

Wallace Ravven | EurekAlert!
Further information:
http://atvb.ahajournals.org/
http://www.ucsf.edu

More articles from Life Sciences:

nachricht Stiffness matters
22.02.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht Separate brain systems cooperate during learning, study finds
22.02.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Stiffness matters

22.02.2018 | Life Sciences

Magnetic field traces gas and dust swirling around supermassive black hole

22.02.2018 | Physics and Astronomy

First evidence of surprising ocean warming around Galápagos corals

22.02.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>