Institute for Genome Sciences and Policy, Durham, NC 27708, USA.
Hepatology. 2010 Jun;51(6):1904-11. doi: 10.1002/hep.23592.
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.
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.
最近,干扰素(IFN)-lambda 基因区域发生的遗传多态性与基于 IFN 的丙型肝炎感染治疗反应相关。丙型肝炎病毒感染和 IFN 治疗均与血清胆固醇降低有关,而高胆固醇与对 IFN 反应增加的可能性相关。我们试图确定 IFN-lambda 基因变异是否也与慢性丙型肝炎患者的血清脂质水平相关。我们比较了位于 IL28 基因近端的 rs12979860 多态性的基因型与 746 名未接受治疗的慢性丙型肝炎病毒感染患者的血清脂质和载脂蛋白水平,使用多变量方差分析。与 CT 或 TT 基因型相比,携带 rs12979860 CC 应答基因型的患者总胆固醇(P = 6.0 x 10(-4))、载脂蛋白 B(P = 1.3 x 10(-6))和低密度脂蛋白(LDL)胆固醇(P = 8.9 x 10(-10))水平显著更高。与 rs12979860 CC 基因型组相比,rs12979860 CC 基因型组的甘油三酯(P = 0.03)、载脂蛋白 A-I(P = 0.06)和载脂蛋白 E(P = 0.01)水平略低,而高密度脂蛋白胆固醇(P = 0.78)和载脂蛋白 C-III(P = 0.74)水平不受 rs12979860 基因型的影响。
我们的结果表明,慢性丙型肝炎患者的 LDL 胆固醇水平较低可能是宿主对丙型肝炎的内源性 IFN 反应的标志物,而 rs12979860 CC 应答基因型的患者可能对病毒的内源性 IFN 反应较低。