Clark, P. J.Thompson, A. J.Zhu, M.Vock, D. M.Zhu, Q.Ge, D.Patel, K.Harrison, S. A.Urban, T. J.Naggie, S.Fellay, J.Tillmann, H. L.Shianna, K.Noviello, S.Pedicone, L. D.Esteban, R.Kwo, P.Sulkowski, M. S.Afdhal, N.Albrecht, J. K.Goldstein, D. B.McHutchison, J. G.Muir, A. J.IDEAL investigators2025-07-072025-07-072012Clark PJ, Thompson AJ, Zhu M, et al. Interleukin 28B polymorphisms are the only common genetic variants associated with low-density lipoprotein cholesterol (LDL-C) in genotype-1 chronic hepatitis C and determine the association between LDL-C and treatment response. J Viral Hepat. 2012;19(5):332-340. doi:10.1111/j.1365-2893.2011.01553.xhttps://hdl.handle.net/1805/49210Low-density lipoprotein cholesterol (LDL-C) levels and interleukin 28B (IL28B) polymorphism are associated with sustained viral response (SVR) to peginterferon/ribavirin (pegIFN/RBV) for chronic hepatitis C (CHC) infection. IL28B has been linked with LDL-C levels using a candidate gene approach, but it is not known whether other genetic variants are associated with LDL-C, nor how these factors definitively affect SVR. We assessed genetic predictors of serum lipid and triglyceride levels in 1604 patients with genotype 1 (G1) chronic hepatitis C virus (HCV) infection by genome-wide association study and developed multivariable predictive models of SVR. IL28B polymorphisms were the only common genetic variants associated with pretreatment LDL-C level in Caucasians (rs12980275, P = 4.7 × 10(-17), poor response IL28B variants associated with lower LDL-C). The association was dependent on HCV infection, IL28B genotype was no longer associated with LDL-C in SVR patients after treatment, while the association remained significant in non-SVR patients (P < 0.001). LDL-C was significantly associated with SVR for heterozygous IL28B genotype patients (P < 0.001) but not for homozygous genotypes. SVR modelling suggested that IL28B heterozygotes with LDL-C > 130 mg/dL and HCV RNA ≤600 000 IU/mL may anticipate cure rates >80%, while the absence of these two criteria was associated with an SVR rate of <35%. IL28B polymorphisms are the only common genetic variants associated with pretreatment LDL-C in G1-HCV. LDL-C remains significantly associated with SVR for heterozygous IL28B genotype patients, where LDL-C and HCV RNA burden may identify those patients with high or low likelihood of cure with pegIFN/RBV therapy.en-USPublisher PolicyCholesterolHepatitis C virusInterleukin 28BLipidsSustained viral responseArticle