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 A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>