Hepatic ISG Expression Is Associated With Genetic Variation in Interleukin 28B and the Outcome of IFN Therapy for Chronic Hepatitis C
Hepatic ISG Expression Is Associated With Genetic Variation in Interleukin 28B and the Outcome of IFN Therapy for Chronic Hepatitis C
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DOI：
10.1053/j.gastro.2010.04.049
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发表时间：
2010-08-01
期刊：
影响因子：
29.4
通讯作者：
Kaneko, Shuichi
中科院分区：
文献类型：
--
作者：
Honda, Masao;Sakai, Akito;Kaneko, Shuichi
背景与目的：聚乙二醇干扰素与利巴韦林联合治疗的治疗反应与多种病毒和宿主因素有关；然而，这些因素的临床相关性和关系尚未得到充分评估。方法：我们研究了168例接受聚乙二醇干扰素和利巴韦林联合治疗的慢性丙型肝炎患者。使用Affymetrix基因芯片（Affymetrix, Santa Clara， CA）分析91例患者肝脏中的基因表达谱。实时聚合酶链反应检测干扰素刺激基因（ISGs）的表达。在91例患者中测定了白细胞介素28B （IL28B; rs8099917）的遗传变异。结果：肝分化患者的基因表达谱分为2组：ISGs上调组和ISGs下调组。在ISGs上调组中，对治疗无反应的患者比例很高（P = 0.002）。多因素logistic回归分析显示，isg (= 2) （OR, 5.09; P = 0.003）与病毒反应密切相关。91例患者的IL28B多态性显示66%为主要纯合子（TT）， 30%为杂合子（TG）， 4%为次要纯合子（GG）。有趣的是，肝脏ISGs与IL28B多态性相关（OR, 18.1; P < .001），且其在次要基因型（TG或GG）患者中的表达明显高于主要基因型（TT）患者。结论：肝脏ISGs的表达与治疗反应和IL28B的遗传变异密切相关。宿主和病毒因子作为预测因子的不同作用也可能存在。
BACKGROUND & AIMS: Multiple viral and host factors are related to the treatment response to pegylated-interferon and ribavirin combination therapy; however, the clinical relevance and relationship of these factors have not yet been fully evaluated. METHODS: We studied 168 patients with chronic hepatitis C who received pegylated-interferon and ribavirin combination therapy. Gene expression profiles in the livers of 91 patients were analyzed using an Affymetrix genechip (Affymetrix, Santa Clara, CA). The expression of interferon-stimulated genes (ISGs) was evaluated in all samples by real-time polymerase chain reaction. Genetic variation in interleukin 28B (IL28B; rs8099917) was determined in 91 patients. RESULTS: Gene expression profiling of the liver differentiated patients into 2 groups: patients with up-regulated ISGs and patients with down-regulated ISGs. A high proportion of patients with no response to treatment was found in the up-regulated ISGs group (P = .002). Multivariate logistic regression analysis showed that ISGs (= 2) (OR, 5.09; P = .003) were strongly associated with the viral response. The IL28B polymorphism of 91 patients showed that 66% were major homozygotes (TT), 30% were heterozygotes (TG), and 4% were minor homozygotes (GG). Interestingly, hepatic ISGs were associated with the IL28B polymorphism (OR, 18.1; P < .001), and its expression was significantly higher in patients with the minor genotype (TG or GG) than in those with the major genotype (TT). CONCLUSIONS: The expression of hepatic ISGs is strongly associated with treatment response and genetic variation of IL28B. The differential role of host and viral factors as predicting factors may also be present.