Interferon-lambda genotype and low serum low-density lipoprotein cholesterol levels in patients with chronic hepatitis C infection

Authors


  • Potential conflict of interest: Study collaborators Arlene Hughes and Michael Mosteller and co-author Stephen Gardner are employed by GlaxoSmithKline. Dr. Thompson is a consultant for Schering-Plough. Dr. McHutchison received grants from Echosers, Idera Pharmaceutical, Intarcia, Medtronic, Osiris Therapeutics, Three Rivers Pharmaceuticals, and ViroChem Pharma. He is a consultant for and received grants from Abbott Laboratories, Biolex, Gilead, GlaxoSmithKline, GlobeImmune, Hoffman-LaRoche, Human Genome Sciences, Intarcia, Merck Group, Novartis, Pfizer, Pharmasset, and Vertex. He is also a consultant for Anadys, Avila, Epiphany Biosciences, and iTheRx.

Abstract

Recently, genetic polymorphisms occurring in the interferon (IFN)-lambda gene region were associated with response to IFN-based treatment of hepatitis C infection. Both infection with the hepatitis C virus and IFN therapy are associated with decreased serum cholesterol and high cholesterol has been associated with increased likelihood to respond to IFN. We sought to determine if the IFN-lambda gene variant was also associated with serum lipid levels in chronic hepatitis C patients. We compared genotypes of the rs12979860 polymorphism, located proximal to the IL28 gene, with serum lipid and apolipoprotein levels in 746 subjects with chronic hepatitis C virus infection, not currently undergoing treatment, using multivariable analysis of variance. Levels of total cholesterol (P = 6.0 × 10−4), apolipoprotein B (P = 1.3 × 10−6) and low-density lipoprotein (LDL) cholesterol (P = 8.9 × 10−10) were significantly higher in subjects carrying the rs12979860 CC responder genotype compared with those with the CT or TT genotype. Levels of triglycerides (P = 0.03), apolipoprotein A-I (P = 0.06), and apolipoprotein E (P = 0.01) were slightly lower in the rs12979860 CC genotype group, whereas levels of high-density lipoprotein cholesterol (P = 0.78) and apolipoprotein C-III (P = 0.74) did not vary by rs12979860 genotype. Conclusion: Our results suggest that low levels of LDL cholesterol in chronic hepatitis C patients may be a marker of host endogenous IFN response to hepatitis C and that subjects with the rs12979860 CC responder genotype may have a lower endogenous IFN response to the virus. HEPATOLOGY 2010

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