CYP4502E1基因多态性及法医学和群体遗传学意义的研究

发布时间：2018-03-04 11:09

本文选题：细胞色素P4502E1(CYP4502E1)　切入点：单核苷酸多态性(SNP)　出处：《中国医科大学》2005年硕士论文　论文类型：学位论文

【摘要】：前言细胞色素P450酶系(Cytochrome P450,CYP450)是一组结构和功能相关的超家族基因编码的同工酶,其特征是与CO结合后在450nm处有吸收峰的含血红素的单链蛋白质。在人类CYP450超基因家族中,主要有三个基因家族CYP4501、CYP4502及CYP4503在体内参与外源生物转化,并已发现人类肝脏中至少有19种CYP450酶参与药物的代谢。大量研究表明,人体内许多药物的代谢存在个体差异,这种差异可能是由遗传和后天双重因素所致。CYP450的合成受着遗传基因的调控,一旦基因发生变异,它所调控合成的CYP450酶及酶所催化的药物代谢即发生变化。因此CYP450酶的多态性是构成药物代谢种族及个体差异的基础。已知在人类的CYP450酶系统中具有遗传多态性的有CYP4501A1、CYP4501A2、CYP4502A6、CYP4502C、CYP4502D6、CYP4502E1及CYP4503A4等,其中研究比较多的是CYP4502E1。 CYP4502E1是二甲基亚硝胺D-脱甲基酶,它主要参与激活小分子致癌物如苯、四氯化碳和亚硝胺等,同时参与酒精的氧化代谢和产生自由基而启动脂质过氧化过程。CYP4502E1主要存在于肝脏,在食管和肺组织也有表达。虽然CYP4502E1受外界因子如酒精的诱导,但不论是诱导前或诱导后其活性水平都有相当大的个体差异,提示其表达是由遗传决定的。许多研究表明CYP4502E1基因多态性与其代谢活性密切相关,并与某些癌症的易感性相关。 CYP4502E1基因位于第10号染色体,共有9个外显子和8个内含子,计11413个碱基。目前报道有5种限制性片段长度多态性(restrict fragment length polymorphism,RFLP)位点,即TaqI、DraI、RsaI、MspI及5′端的RsaI/PstI。其中DraI和5′端Rsal/PstI将影响CYP2E1的表达。DraI多态性位点
[Abstract]:Foreword. Cytochrome P450 (Cytochrome P450) is a group of structural and functional related superfamily genes encoding isozymes characterized by a heme-containing single-stranded protein with a absorption peak at 450 nm after CO binding. Three major gene families, CYP4501CYP 4502 and CYP4503, are involved in exogenous biotransformation in vivo, and at least 19 CYP450 enzymes have been found to be involved in the metabolism of drugs in the human liver. A large number of studies have shown that there are individual differences in the metabolism of many drugs in the human body. This difference may be caused by both genetic and acquired factors. The synthesis of CYP450 is regulated by genetic genes, and once the genes are mutated, Therefore, the polymorphism of CYP450 enzyme is the basis of the racial and individual differences in drug metabolism. It is known that CYP4501A1, CYP4502A2, CYP4502A6, CYP4502CCYP4502D6, CYP4502E1 and CYP4503A4, are known to have genetic polymorphisms in the human CYP450 enzyme system. CYP4502E1. CYP4502E1 is a D- demethylase of Dimethylnitrosamine, which is mainly involved in the activation of small carcinogens such as benzene, carbon tetrachloride and nitrosamine, and in the oxidative metabolism of alcohol and the production of free radicals. CYP4502E1 is mainly present in the liver. Although CYP4502E1 is induced by external factors such as alcohol, its activity levels vary considerably before and after induction. Many studies have shown that the polymorphism of CYP4502E1 gene is closely related to its metabolic activity and associated with the susceptibility of some cancers. The CYP4502E1 gene is located on chromosome 10, with 9 exons and 8 introns. There are 5 restriction fragment length polymorphisms, strict fragment length polymorphisms, RFLPs. The Rsai / PstI of the 5 'end and the RsaI / PST I of the 5' end of Taq Igna Drai, in which DraI and 5 'end Rsal/PstI will affect the expression of CYP2E1. Drai polymorphism.
【学位授予单位】：中国医科大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：D919.1

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