Duke University Medical Center researchers say that a single-letter change, a C instead of a T, in a tiny segment of DNA near the IL28B gene affects response to hepatitis C treatments. Their work also sheds light on why there are differing rates of response among racial and ethnic groups.
The findings were published August 16 in Nature online in a paper titled “Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance.” The study was funded by the Schering-Plough Research Institute. Schering-Plough has multiple drug candidates in development for the treatment of HCV.
The investigators studied 1,671 individuals who participated in the IDEAL study, a multicenter trial that compared the effect of using ribavirin and peginterferon among patients with the most common form of the disease in the U.S. and Europe.
They found that the patients who had the single-letter change in their DNA were significantly more likely to respond to treatment than those who did not have it. “Eighty percent of those with the favorable response genotype eradicated the virus, while only about 30 percent with the less favorable response genotype did so,” says David Goldstein, Ph.D., senior author and director of the Center for Human Genome Variation in Duke's Institute for Genome Sciences & Policy.
The so-called good genotype proved beneficial to patients in all population subgroups, Dr. Goldstein adds. “But because it appears significantly more often among Caucasian populations than it does among African populations, we feel it explains much of the difference in response rates we see between African Americans and those of European ancestry.”
Researchers found that African Americans with the favorable (CC) genotype had a significantly higher rate of response to treatment (53.3%) than individuals of European ancestry who had the less favorable (TT) genotype (33.3%).
The researchers also ran tests to see if the presence of the biomarker was related in any way to viral load and found a significant association in all groups. “Interestingly, we found that the C allele, although associated with better treatment response, was associated with a higher viral load at baseline, something we have traditionally viewed as a negative prognostic marker when it comes to treatment response,” explains John McHutchison, M.D., study co-author, associate director of the Duke Clinical Research Institute, and a member of the division of gastroenterology in the School of Medicine.
Dr. McHutchison thus suggests that patients who have the beneficial genetic marker might be especially adept at spontaneously clearing the virus through some as yet unknown mechanism.