Most individuals who become infected with hepatitis C virus (HCV) develop a chronic infection, which puts them at risk for cirrhosis and hepatocellular carcinoma [1
]. Single-nucleotide polymorphisms (SNPs) rs12979860 and rs8099917, which are located near IL28B
and in linkage disequilibrium, have been associated with spontaneous HCV clearance and response to treatment of chronic hepatitis C [2
]. The identity of the functional variant underlying these associations and the specific functional mechanism are unknown.
The best genetic model to represent the association between IL28B
genotype and HCV clearance is unclear. Some authors have used a recessive genetic model that compares those with beneficial genotype IL28B
rs12979860-CC with those with either rs12979860-CT or rs12979860-TT [3
]. Other reports have suggested an additive model [6
] or assumed no genetic model [8
]. The association between IL28B
genotype and HCV clearance is robust; therefore, the best genetic model was not critical for discovery studies. However, investigations of the functional mechanism underlying the IL28B
genotype association may benefit from knowledge of the optimal genetic model, and, if IL28B
genotype is used to guide treatment for patients with chronic hepatitis C, the best genetic model should be the basis for such decisions. We have examined alternative genetic models for the association of IL28B
genotype and spontaneous HCV clearance among HCV-infected injection drug users (IDUs) enrolled in the Urban Health Study (UHS).