Interferon-Lambda Genotype and Low Serum Low-Density Lipoprotein Cholesterol Levels in Patients With Chronic Hepatitis C Infection

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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