表观遗传调控是一种不涉及DNA序列变化的可遗传的基因表达方式的改变，DNA甲基化修饰是最常见的表观遗传现象之一，已证实多种基因通过DNA甲基化实现组织特异性表达或参与肿瘤发生。CYP2C19是人体内重要的药物代谢酶之一，研究证实CYP2C19只在肝脏与肝癌组织中表达，并且其表达量的提高与肝癌的发生有一定的关系，但目前对CYP2C19的表达调控研究尚不能对上述现象做出解释。CYP450家族是受表观遗传机制调控的一大类基因，结合近年来CYP450家族的表观研究现状，我们推测DNA甲基化在CYP2C19的表达调控中发挥着重要的作用。本研究将进行体外细胞培养，并采集新鲜的癌组织和癌旁组织标本进行分析，通过5-aza-dC处理细胞、qRT-PCR、BSP等实验手段比较CYP2C19的mRNA与DNA甲基化水平之间的关系，并确定关键的甲基化位点或区域，以阐明DNA甲基化对CYP2C19的表达调控作用。

Epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. DNA methylation, which is the most common epigenetic phenomenon, alters gene expression by way of causing changes in chromatin structure, DNA conformation and DNA-protein interactions. Studies have shown that multiple genes achieve tissue-specific expression or participate in tumorigenesis by DNA methylation. CYP2C19 is an important human drug-metabolizing enzyme with its expression under the regulation of a number of transcriptional factors. It has been confirmed that CYP2C19 is highest expressed in hepatoma tissue and followed by normal liver tissue, which indicates a certain relationship between the increasd CYP2C19 level and carcinogenesis. Tissue-specific expression is one of its traits since CYP2C19 is not expressed in any other tumor or normal tissue. However, current knowledge of CYP2C19 is not sufficient to give explaination to such phenomenon. Cytochrome P 450 superfamily is a large group of enzymes which is under control of epigenetic mechanisms. Combining with the rencent epigenic studies on CYPs, we speculate that DNA methylation also plays an important role in the regulation of CYP2C19. In this study, hepatoma and other cancer cells cultured in vitro will be treated with 5-aza-dC while a variety of newly collected tumor tissue and paired adjacent normal tissue samples are analyzed. We will take advantage of qRT-PCR, bisulfite sequencing PCR（BSP）and other experimental methods to reveal the relationship between CYP2C19 level and DNA methylation.In addition, we will also endeavour to identify the key sites of DNA methylation so that the regulatory factors of CYP2C19 could be further clarified.