IL28B 基因变异对 HIV 和丙型肝炎病毒合并感染患者聚乙二醇干扰素联合利巴韦林治疗反应的预测。
Prediction of response to pegylated interferon plus ribavirin by IL28B gene variation in patients coinfected with HIV and hepatitis C virus.
机构信息
Unit of Infectious Diseases, Hospital Universitario de Valme, Seville, Spain.
出版信息
Clin Infect Dis. 2010 Oct 1;51(7):788-95. doi: 10.1086/656235.
BACKGROUND
Variation in the IL28B gene is associated with sustained virologic response (SVR) to pegylated interferon plus ribavirin in hepatitis C virus (HCV)-monoinfected patients with genotype 1. Data on other genotypes and on patients coinfected with human immunodeficiency virus (HIV) and HCV are more limited. We aimed to assess the predictive ability of variations in the single-nucleotide polymorphism rs12979860 for SVR in HIV/HCV-coinfected patients, regardless of HCV genotype.
METHODS
The rs12979860 genotype was determined by polymerase chain reaction in 154 patients who had received therapy against HCV with pegylated interferon plus ribavirin.
RESULTS
rs12979860 genotype was TT in 20 patients (13%), TC in 66 patients (43%), and CC in 68 patients (44%). Rates of SVR in patients with genotype CC and in those with genotype TC or TT, according to HCV genotype, were, respectively, 50% and 17% (P < .001) in patients with genotype 1, 80% and 25% (P = .027) in patients with genotype 4, and 93% and 77% (P = .115) in patients with genotype 3. The median (interquartile range) low-density lipoprotein cholesterol level in patients with rs12979860 CC was 89 mg/dL (73-120 mg/dL) versus 75 mg/dL (55-91 mg/dL) (P = .001) in those with TC or TT. Independent predictors of SVR were HCV genotype 2-3 (odds ratio [OR], 13.98; 95% confidence interval [CI], 4.87-40.1; P < .001), rs12979860 CC (OR, 5.05; 95% CI, 2.04-12.5; P < .001), baseline plasma HCV RNA load of < or =600,000 IU/mL (OR, 1.99; 95% CI, 1.18- 3.34; P = .009), and female sex (OR, 4.28; 95% CI, 1.08-16.96; P = .039).
CONCLUSIONS
IL28B gene variations independently predict SVR in HIV/HCV-coinfected patients with HCV genotype 1 and non-genotype 1 HCV infection. The association between rs12979860 and plasma low-density lipoprotein cholesterol suggests that the system low-density lipoprotein ligand/receptor might be involved in the effect of this genotype.
背景
白细胞介素 28B 基因的变异与丙型肝炎病毒（HCV）感染患者接受聚乙二醇干扰素加利巴韦林治疗后的持续病毒学应答（SVR）相关。关于其他基因型和感染人类免疫缺陷病毒（HIV）和 HCV 的患者的数据则更为有限。我们旨在评估单核苷酸多态性 rs12979860 对 HIV/HCV 合并感染患者 SVR 的预测能力，而不论 HCV 基因型如何。
方法
在 154 例接受聚乙二醇干扰素加利巴韦林治疗 HCV 的患者中，通过聚合酶链反应确定 rs12979860 基因型。
结果
rs12979860 基因型分别为 TT 型 20 例（13%）、TC 型 66 例（43%）和 CC 型 68 例（44%）。根据 HCV 基因型，CC 基因型患者和 TC 或 TT 基因型患者的 SVR 率分别为基因型 1 患者中的 50%和 17%（P <.001）、基因型 4 患者中的 80%和 25%（P =.027）和基因型 3 患者中的 93%和 77%（P =.115）。rs12979860 CC 患者的中位（四分位间距）低密度脂蛋白胆固醇水平为 89mg/dL（73-120mg/dL），而 TC 或 TT 患者为 75mg/dL（55-91mg/dL）（P =.001）。SVR 的独立预测因子包括 HCV 基因型 2-3（比值比[OR]，13.98；95%置信区间[CI]，4.87-40.1；P <.001）、rs12979860 CC（OR，5.05；95%CI，2.04-12.5；P <.001）、基线血浆 HCV RNA 载量<或=600,000IU/mL（OR，1.99；95%CI，1.18-3.34；P =.009）和女性（OR，4.28；95%CI，1.08-16.96；P =.039）。
结论
白细胞介素 28B 基因变异独立预测 HIV/HCV 合并感染患者 HCV 基因型 1 和非基因型 1 HCV 感染的 SVR。rs12979860 与血浆低密度脂蛋白胆固醇之间的关联提示，该基因型可能涉及系统低密度脂蛋白配体/受体。
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