Interferon Lambda 4 Phenotypes
A collaboration led by DCEG investigators in the Infections and Immunoepidemiology Branch (IIB) and the Laboratory of Translational Genomics (LTG) led to the discovery of the interferon lambda 4 (IFNL4) gene (Prokunina-Olsson L, Muchmore B, Tang W, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet 2013). Recent epidemiological studies have associated IFNL4 genotype with hepatic inflammation and fibrosis, which are precursors of hepatocellular carcinoma (HCC), as well as mucinous ovarian carcinoma, a rare cancer subtype of uncertain etiology. Evidence of strong evolutionary selection against the IFNL4-ΔG allele suggests IFNL4 could impact diseases besides HCV infection; recent studies in mice demonstrated that the interferon lambda family plays an important role in a wide range of infections. Taken together, these findings make IFNL4 a candidate gene for many infections and conditions.
IIB researchers have initiated investigations to examine the phenotypic range of the IFNL4 genotype, including studies of: hepatic inflammation and fibrosis, which are precursors of hepatocellular carcinoma; mucinous ovarian carcinoma; opportunistic infections and malignancies; and neuroinvasive West Nile virus infection. In addition, they plan a phenome-wide association study for the IFNL4 genotype among patients enrolled in a large managed care organization.
For more information, contact Thomas O’Brien.