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, 51 (6), 1904-11

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

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

Josephine H Li et al. Hepatology.

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 x 10(-4)), apolipoprotein B (P = 1.3 x 10(-6)) and low-density lipoprotein (LDL) cholesterol (P = 8.9 x 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.

Figures

Figure 1
Figure 1. Differences in LDL cholesterol, apolipoprotein B levels, and total cholesterol by HCV genotype in patients with chronic HCV infection
Panel (A) LDL cholesterol; Panel (B) Apolipoprotein B; Panel (C) Total cholesterol. Means and standard error bars shown, adjusted for cohort, age, sex, and race.
Figure 2
Figure 2. Effect of rs12979860 genotype (CC versus TT/TC) on levels of LDL cholesterol and apolipoprotein B, stratified by HCV genotype (gt 1, gt 2, gt 3)
Panel (A) LDL cholesterol (LDL-C); Panel (B) Apolipoprotein B. Means and standard error bars shown, adjusted for cohort, age, sex, and race. Pooled analysis was additionally controlled for HCV genotype.

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