Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers find gene variants that cause stent thrombosis in people with coronary artery disease

26.10.2011
In a first-of-its-kind study, researchers from Mount Sinai School of Medicine have discovered several gene variants contributing to early stent thrombosis (ST), a devastating and often deadly complication after coronary stent implantation in people with coronary artery disease.

The team found that three of these variants were associated with impaired sensitivity to the common blood thinner clopidogrel, and a fourth that affects a blood platelet receptor involved in platelet aggregation and clot formation. Analyzing these gene variants will help researchers identify patients at risk for early stent thrombosis and take measures to prevent it.

The data also provide a clinical and genomic score that indicates the best predictive accuracy for stent thrombosis risk. The findings are published in the Oct. 26 issue of the Journal of the American Medical Association.

Through a partnership with the Institut de Cardiologie at Pitié-Salpêtrière University Hospital in Paris, France, the research team evaluated the DNA of 123 patients who had undergone stent implantation and developed early ST while treated with dual antiplatelet therapy, which is a combination of aspirin and clopidogrel. The patient information was shared as part of ONline ASSIstance for Stent Thrombosis (ONASSIST), a nationwide web registry of patients in France.

Looking at 23 genetic variants previously associated with clopidogrel metabolism, platelet receptor function, and the control of blood clotting, they found four that were predictive risk factors of early ST. They also found that a low dose of clopidogrel in combination with a proton pump inhibitor, which is a drug to treat acid reflux, also increased the risk of early ST.

"Our research indicates that early stent thrombosis is strongly related to ineffectiveness of clopidogrel in certain patients," said Jean-Sebastien Hulot, MD PhD, Associate Professor of Medicine in the Division of Cardiology and Director Pharmacogenomics and Personalized Therapeutics at the Cardiovascular Research Center at Mount Sinai School of Medicine. "Now that we have a clearer understanding of the mechanism behind the development of stent thrombosis, we can take preventive measures to protect our patients from this deadly complication."

The research team compared the genetic code of people registered in the ONASSIST program with 246 coronary patients without early ST. They evaluated alleles, which are types of genetic variation that arise from mutations, of 23 genes. They found that CYP2C19*2 allele, which is commonly associated with loss of enzyme function, was highly prevalent in people presenting with early ST, as was the allele ABCB1 3435T, and both were infrequent in the control group. Two other alleles, CYP2C19*17 and ITGB3, were prevalent in the healthy control group but not in the early ST group indicating a protective effect. The scientists developed a genetic score where the more of these mutations that the patient had, the higher their risk for developing early ST. This risk was independent of clinical risk factors, including the use of proton pump inhibitors, acuteness of PCI, complexity of cardiac lesions, left ventricular heart function, and a high dose of clopidogrel. Only two of these risk factors– clopidogrel dose and proton pump inhibitor use – are modifiable in reducing risk for early ST. Eventually, the best prediction was achieved using the combination of both clinical and genetic factors. The authors conclude that this "clinico-genomic" approach could be useful prior to stent implantation to identify the patients with high-ST risk.

"We found that, independent of other clinical risk factors, these genetic factors play a critical role in the development of early ST," said Dr. Hulot. "Altogether, our data will help clinicians understand the factors contributing to early ST, and allow them to reduce the outcome risk to these patients. Understanding the genetic factors provides researchers with new drug targets for future study to reduce the genetic risk as well."

Mount Sinai's Cardiovascular Research Center plans to continue the partnership with the Institut de Cardiologie at Pitié-Salpêtrière University Hospital in Paris to develop an international cardiogenomic laboratory to better understand genetic risk factors associated with heart disease and treatments for heart disease to improve and better target clinical care for patients.

PCI is a minimally invasive technique used to treat patients with diseased coronary arteries caused by a buildup of plaque and cholesterol. During the procedure, a catheter is threaded through the body, typically from an artery in the groin to a blocked or occluded vessel in the heart. The occlusion is removed and a stent is often inserted to maintain flow within the blood vessel. Up to four percent of patients undergoing PCI experience early ST, which is deadly in 40 percent of those patients.

Mount Sinai Press Office | EurekAlert!
Further information:
http://www.mssm.edu

More articles from Health and Medicine:

nachricht Satellites, airport visibility readings shed light on troops' exposure to air pollution
09.12.2016 | Veterans Affairs Research Communications

nachricht Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>