Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Enzyme deficiency protects hepatitis C patients from treatment-related anemia

22.02.2010
Many people who undergo treatment for hepatitis C develop hemolytic anemia, a disorder that destroys red blood cells.

In some cases, it is so severe they have to reduce their medication or stop therapy altogether. But now, scientists in Duke University's Institute for Genome Sciences & Policy (IGSP) have discovered two genetic alterations linked to a benign enzyme condition that keep some patients anemia-free.

They say the discovery, appearing online in the journal Nature, opens the door to treatment for patients who have never been considered candidates for therapy before and may also hold the key to new drugs that could prevent anemia from developing in the first place.

The protective mechanism is a deficiency in a gene called ITPA. "We found that patients who carried specific functional variants are strongly protected against developing anemia," says David Goldstein, Ph.D., director of the Center for Human Genome Variation in the IGSP and a senior author of the study.

Previous studies had identified the genetic variants as the cause of a deficiency in the production of an enzyme, inosine triphosphatase. But it was only through a genome-wide association study that the Duke team was able to show that these same variants were protective against anemia induced by ribavirin, one of two necessary drugs in hepatitis C treatment.

About 180 million people world-wide are infected with the hepatitis C virus, and about 30 to 40 percent of them could develop some degree of treatment-related anemia, according to John McHutchison, M.D. associate director for research at the Duke Clinical Research Institute and also a senior author. "It's a big problem. Hemolytic anemia reduces the level of hemoglobin in the blood and robs it of its ability to carry oxygen. Anything that could help us predict who is going to become anemic and who is not could help us better manage therapy and give all patients the best chance of a good outcome."

Goldstein and McHutchison, who had earlier worked together in identifying genetic variants that helped explain race-based differences in response to hepatitis C treatments, believed there was probably a gene-based solution to the anemia puzzle as well.

Working with first authors Jacques Fellay, M.D.; Alex Thompson, M.D., PhD.; and Dongliang Ge, Ph.D., investigators turned to a rich database already at hand: the records of 1286 individuals who had earlier taken part in the IDEAL study, a large, randomized, Duke-led clinical trial that compared leading therapies for hepatitis C.

Researchers separated the patients into three ethnic groups, (988 European Americans, 198 African Americans, and 100 Hispanic Americans) and analyzed their decline in hemoglobin levels during the first month of treatment.

The researchers conducted a genome-wide association study and found several polymorphisms - single-letter DNA alterations - also known as "SNPs or "snips" –associated with reduced hemoglobin levels. But finding an association is just a start: of more biological importance is the identification of the causal variants, the polymorphisms that directly influence hemoglobin levels. Investigators discovered that the two variants known to cause ITPA deficiency appeared almost exclusively on chromosomes that also carried the protective version of the most associated SNP. Further statistical analysis proved that the two variants were indeed the source of protection from anemia.

McHutchison says the discovery is clinically important. "The beauty of this finding is that it may mean we could consider offering treatment to patients who have additional problems, like coronary artery disease or kidney disease. Right now, we are generally uncomfortable treating these patients because anemia could make their underlying condition worse. If a test could tell us which patients are not going to become anemic, we could consider treating them."

"Most of us trace the birth of pharmacogenetics to a 1957 paper by Arno Moltulsky who argued that important drug responses may often depend on genetic differences among people that are invisible until an individual takes a certain drug," says Goldstein. "These ITPA variants reflect this classic formulation of pharmacogenetics, and suggest to us that there are many other important variants that can and should be found through the careful genetic analyses of patients' drug responses."

Colleagues from Duke who contributed to the study include Curtis Gumbs, Thomas Urban, Kevin Shianna, Latasha Little and Andrew Muir. Other co-authors include Mark Sulkowski, from Johns Hopkins; and Ping Qiu, Arthur Bertelsen, Mark Watson, Amelia Warner, Clifford Brass and Janice Albrecht, from Schering-Plough Research Institute.

Schering-Plough Research Institute funded the study and has filed a patent application based on the findings. Ten of the study authors, including Goldstein, Thompson, Ge, Fellay, Urban, Shianna and McHutchison, are listed as inventors on the application.

Michelle Gailiun | EurekAlert!
Further information:
http://www.duke.edu

Further reports about: Genom IGSP ITPA McHutchison SNP enzyme genetic variant hemoglobin levels hepatitis C treatment

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

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 >>>