Discovering a new hepatitis C gene—and its implications for precision medicine

2013

Challenge

Hepatitis C viral (HCV) infection represents a serious threat to public health: up to 150 million individuals are infected worldwide, and as many as 85 percent will develop chronic hepatitis C . Up to five percent of those with chronic hepatitis C may eventually die from liver disease or cancer . Historically, individuals of African descent are less likely to respond to HCV treatment than patients of European or Asian ancestry, suggesting a genetic component to this treatment outcome.

Advance

IRP investigators Ludmila Prokunina-Olsson, Ph.D., and Thomas O’Brien, M.D., M.P.H., used RNA sequencing to uncover a new gene, Interferon lambda 4 (IFNL4), that affects the body’s ability to overcome HCV infection. Only individuals who carry a specific inherited genetic variant of IFNL4 can produce the IFN-λ4 protein, which is strongly associated with a reduced ability to clear the viral infection from the body.

Impact

The gene discovery may help researchers better understand why some people’s immune systems do not respond as strongly as others’ to clear HCV. In addition, the new genetic marker may better predict HCV treatment outcomes for African-American patients than currently available tests, offering a potential mechanism to improve care in this population and reduce existing health disparities.

Publications

Prokunina-Olsson L, Muchmore B, Tang W, Pfeiffer RM, Park H, Dickensheets H, Hergott D, Porter-Gill P, Mumy A, Kohaar I, Chen S, Brand N, Tarway M, Liu L, Sheikh F, Astemborski J, Bonkovsky HL, Edlin BR, Howell CD, Morgan TR, Thomas DL, Rehermann B, Donnelly RP, O'Brien TR. (2013). A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet. 45(2), 164-71.

National Cancer Institute press release – http://www.cancer.gov/newscenter/newsfromnci/2013/IFNL4affectsclearanceofhepatitisCvirus