中国大陆汉族人群CYP3A4 基因变异分析

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (3): 300-304.

中国大陆汉族人群CYP3A4 基因变异分析

黄敏, 汪晖, 平洁, 刘志苏¹

武汉大学基础医学院药理学系;
¹武汉大学中南医院普外科,武汉 430071,湖北

收稿日期:2005-11-02 修回日期:2006-03-01 出版日期:2006-03-26 发布日期:2020-12-04
通讯作者: 汪晖,女,教授,博士生导师,主要从事生化药理与药物代谢研究。Tel:027-68758665Fax:027-87731670 E-mail:clbwhcbd@yahoo.com
作者简介:黄敏,女,药理学博士生,主要从事生化药理与药物代谢研究。
基金资助:
武汉大学预研基金资助项目(No301270050) 和教育部留学人员回国启动基金(2004)

Genetic Polymorphism of human CYP3A4 gene in population of Han nationality in China

HUANG Min, WANG Hui, PING Jie, LIU Zhi-su¹

Department of Pharmacology,Basic Medical College of Wuhan University;
¹Department of General Surgery,Zhongnan Hospital of Wuhan University,Wuhan 430071,Hubei,China

Received:2005-11-02 Revised:2006-03-01 Online:2006-03-26 Published:2020-12-04

摘要/Abstract

摘要： 目的研究中国大陆汉族人群中细胞色素P4503A4(CYP3A4)的基因变异及其分布。方法 140例血样本来自中国大陆25个省份的汉族人口,用聚合式酶链反应-非放射性单链构象多态性(PCR-SSCP)-直接测序方法检测CYP3A4基因的变异。结果中国大陆汉族人群存在CYP3A4基因内含子2T4127G变异。140例人群中有31人存在此变异,变异频率为22.1%。中国大陆汉族人群未发现CYP3A4基因13个外显子的变异。结论中国大陆汉族人群CYP3A4基因存在内含子2的多态性分布,其基因变异不同于其他种族。

关键词: 细胞色素P4503A4, 基因变异, PCR-SSCP, DNA测序, 汉族

Abstract: AIM: To investigate the distribution of cytochrome P450 3A4 (CYP3A4) genetic polymorphism in population of Han nationality of mainland in China.METHODS: Genomic DNA was extracted from 140 mainland Chinese peripheral blood,then polymerase chain reaction-single strand conformation polymorphism (PCRSSCP)combined with silver staining and DNA sequencing were used to detect mutations in CYP3A4 gene.RESULTS: In the population,a novel mutation in intron 2 of CYP3A4 gene was detected in 31 out of 140 persons.The frequency of intronic mutation in CYP3A4 gene was 22.1%.No mutation was found either in 5′proximal regulating region or in 13 exons of CYP3A4 gene.CONCLUSION: There is a novel mutant allele in CYP3A4 gene in population of Han nationality of mainland in China.It is different from those in other ethnic groups.

Key words: CYP 3A4 gene, genetic mutation, PCRSSCP, DNA sequencing, Han nationality

中图分类号:

R966

黄敏, 汪晖, 平洁, 刘志苏. 中国大陆汉族人群CYP3A4 基因变异分析[J]. 中国临床药理学与治疗学, 2006, 11(3): 300-304.

参考文献

1 Nelson DR,Kamataki T,Waxman DJ,Guengerich FP,Estabrook RW,Feyereisen R,et al.The P450 superfamily:update on new sequence,gene mapping,accession numbers,early trivialnames of enzymes and nomenclature[J].DNA Cell Biol,1993;12:1-51
2 Hashimoto H,Toide K,Kitamura R,Fujita M,Tagawa S,Itoh S,et al.Gene structure of CYP3A4,an adult-specific form of cytochrome P450 in human livers,and its transcriptional control[J].Eur J Biochem,1993;218:585-95
3 Rebbeek TR,Jaffc JM,Walker AH,Wein AJ,Malkowicz SB.Modification of clinical presentation of prostate tumors by a novel genetic variant in CYP3A4[J].J Natl Cancer Inst,1998;90:1125-229
4 Westlind A,Lofberg L,Tindberg N,Andersson TB,Ingelman-Sundberg M.Interindividual differences in hepatic expression of CYP3A4:relationship to genetic polymorphism in the 5' -upstream regulatory region[J].Biochem Biophys Res Commen,1999;259:201-5
5 Sata F,Sapone A,Elizondo G,Stocker P,Miller VP,Zheng W,et al.CYP3A4 allelic variants with amino acid substitution in exons 7 and 12:evidence for an allelic variant with altered catalytic activity[J].Clin pharmacol Ther,2000;7:48-56
6 Hsieh KP,Lin YY,Cheng CL,LaiML,Lin MS,Siest JP,et al.Novel mutations of the CYP3A4 in Chinese[J].Drug Metab Dispos,2001;29:268-73
7 Eiselt R,Domanski TL,Zibat A,Mueller R,Presecan-Siedel E,Hustert E,et al.Identification and functional characterizations of eight CYP3A4 protein variants[J].Pharmagenetics,2001;11:447-58
8 Lamba JK,Lin YS,Thummel K,Daly A,Watkins PB,Strom S,et al.Common allelic variants of cytochrome P4503A4 and their prevalence in different populations[J].Pharmacogenetics,2002;12:121-32
9 Hamzeiy H,Mashhadian NV,Edwards HJ,Goldfarb PS.Mutation analysis of human CYP3A4 gene 5′- regulatory region:population screening using non-radioavtive SSCP[J].Mutat Res,2002;500:103-10
10 Kuehl P,Zhang J,Lin Y,Lamba J,Assem M,Schuetz J,et al.Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression[J].Nat Genet,2001;27:383-91
11 Cheesman MJ,Reilly PE.Differential inducibility of specific mRNA corresponding to five CYP3A isoforms in female rat liver by RU486 and food deprivation:Comparison with protein abundance and enzymatic activities[J].Biochem Pharmacol,1998;56:473-81

[1]	李宝群, 沈杰, 周宏灏. 维生素D受体变异对下游靶基因转录调控的研究进展[J]. 中国临床药理学与治疗学, 2009, 14(8): 941-945.
[2]	李维亮, 辛华雯, 吴笑春, 李罄, 熊磊. 中国汉族人三磷酸肌苷焦磷酸酶活性的分布[J]. 中国临床药理学与治疗学, 2009, 14(4): 426-431.
[3]	尹继业, 刘昭前. ABCC家族基因变异性研究进展[J]. 中国临床药理学与治疗学, 2008, 13(2): 220-227.
[4]	范志刚, 张虹, 张玉萍, 李进文, 夏尚全. 新疆维族与汉族肾移植后环孢素A血药浓度分析[J]. 中国临床药理学与治疗学, 2001, 6(2): 152-153.