CAJ | 학술논문

α干扰素，包括长效干扰素———聚乙醇化α干扰素（PEG‐IFNα），是临床用以治疗慢性乙型肝炎的首选药物。但干扰素治疗通常只能在有限的患者中获得完全应答。目前干扰素治疗应答相关指标预测的灵敏度与特异度远未令人满意，因此继续寻找潜在的与干扰素疗效预测相关的分子标记仍是一个十分有意义的工作。为探讨慢性乙型肝炎患者基因组 DNA甲基化状态与干扰素治疗疗效的关系，本研究采用 Roche‐NimbleGen人甲基化DNA免疫共沉淀‐芯片（MeDIP‐chip）技术，分析20例不同干扰素疗效慢性乙型肝炎患者的血浆基因组启动子甲基化谱差异，并利用MeDIP‐定量聚合酶链反应（MeDIP‐qPCR ）检验部分基因启动子区域DNA甲基化的水平。结果显示，与快速应答组相比，无应答组中有588个基因启动子区甲基化水平存在显著差异（P＜0．05）。这些基因主要涉及多个信号通路，即钙离子信号通路、细胞周期调节通路、肝脏代谢相关通路等。MeDIP‐qPCR验证与芯片结果的一致性超过80％。本研究为探讨差异甲基化基因在干扰素应答中的作用及发现潜在的预测干扰素疗效的血液分子标记奠定了基础。
α간우소，포괄장효간우소———취을순화α간우소（PEG‐IFNα），시림상용이치료만성을형간염적수선약물。단간우소치료통상지능재유한적환자중획득완전응답。목전간우소치료응답상관지표예측적령민도여특이도원미령인만의，인차계속심조잠재적여간우소료효예측상관적분자표기잉시일개십분유의의적공작。위탐토만성을형간염환자기인조 DNA갑기화상태여간우소치료료효적관계，본연구채용 Roche‐NimbleGen인갑기화DNA면역공침정‐심편（MeDIP‐chip）기술，분석20례불동간우소료효만성을형간염환자적혈장기인조계동자갑기화보차이，병이용MeDIP‐정량취합매련반응（MeDIP‐qPCR ）검험부분기인계동자구역DNA갑기화적수평。결과현시，여쾌속응답조상비，무응답조중유588개기인계동자구갑기화수평존재현저차이（P＜0．05）。저사기인주요섭급다개신호통로，즉개리자신호통로、세포주기조절통로、간장대사상관통로등。MeDIP‐qPCR험증여심편결과적일치성초과80％。본연구위탐토차이갑기화기인재간우소응답중적작용급발현잠재적예측간우소료효적혈액분자표기전정료기출。
Interferonα (IFN‐α) therapy remains a mainstay of treatment of chronic hepatitis B .However , sustained remission rates remain relatively low ,and the search for factors important for response to therapy continues .In order to study the relationship between the genomic DNA methylation profile and response to interferon therapy in chronic hepatitis B ,pretreatment plasma samples of 20 patients with chronic hepatitis B (CHB) receiving pegylated interferon α (PEG‐IFNα) treatment were subjected to DNA methylation analyses using Roche‐NimbleGen Human DNA Methylation 2 .1M Deluxe Promoter v2 Array .Methylated DNA immunoprecipitation‐quantitative polymerase chain reaction (MeDIP‐qPCR ) was used to further validate the methylation status of specific genes . A total of 588 genes were found to show differential methylation in interferon nonresponse group as compared with the rapid response group .These differential methylated genes were involved in several signaling pathways ,such as the calcium signaling pathway ,cell cycle and liver metabolism .The methylation levels of several genes in the two groups were confirmed by MeDIP‐qPCR ,consistent with the results of the MeDIP‐chip study . Our data provide a foundation for future study on the functions of differential methylated genes in interferon response as well as the discovery of new molecular markers for predicting prognosis of interferon therapy in CHB patients .