NIH researchers discover gene that affect hepatitis C clearance

Scientists with the National Institutes of Health's National Cancer Institute recently discovered a gene that interferes with the clearance of infection with the hepatitis C virus.

The researchers also found that an inherited variant within the gene, Interferon Lambda 4, predicts how patients respond to hepatitis C infection treatment. The team used an RNA sequencing technology to explain the why some people experience spontaneous virus clearance and certain treatment response.

"By using RNA sequencing we looked outside the box to search for something beyond what was already known in this region," Ludmila Prokunina-Olsson, the co-lead investigator of the study, said. "We hit the jackpot with the discovery of a new gene. It is possible that other important genes may be discovered using this approach."

Scientists previously identified common inherited genetic markers connected to hepatitis C treatment response located on chromosome 19 near the known interferon gene IFNL3. The researchers found that the IFNL4 region harbors two potential variants. One variant, deltaG, produces a protein, IFNL4 protein, that is connected with poorer clearance and response to hepatitis C, than the alternate variant. The new gene may explain why African-Americans have a lower response to current hepatitis C treatments that patients of European and Asian ancestry.

"Our work fulfills several promises of the genomic era," Thomas R. O'Brien, a scientist with the DCI, said. "One, a better understanding of biology; two, personalized medicine; and three, new potential treatments. We deliver immediately on the first two. We've identified a new gene that may help us better understand response to viral infection and the new genetic marker may transition to clinical practice because it predicts treatment outcome for African-American patients better than the current genetic test. For the third, the INFL4 protein may be used as a novel therapeutic target for hepatitis C virus infection, and possibly other diseases."

Future studies will explore the molecular function of the IFNL 4 protein in normal and disease conditions.