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Enzyme deficiency protects hepatitis C patients from treatment-related anemia
Date:2/21/2010

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 treat
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Contact: Michelle Gailiun
michelle.gailiun@duke.edu
919-724-5343
Duke University Medical Center
Source:Eurekalert

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