广东人群 CYP3A4基因rs28371759(20070T>C)位点多态性调查

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (11): 1255-1258.

广东人群 CYP3A4基因rs28371759(20070T>C)位点多态性调查

王瑢, 陈珂蕊, 刘晓媚, 唐惠恩, 何震宇

广东药学院基础学院,生物化学与分子生物学系,广州 510006,广东

收稿日期:2013-07-22 修回日期:2014-11-03 出版日期:2014-11-26 发布日期:2014-12-09
通讯作者: 何震宇,男,博士,副教授,硕士生导师,研究方向:分子诊断。 E-mail: jdbshzy@163.com
作者简介:王瑢,女,2011级硕士生,研究方向:药物基因组学。 Tel: 15899871910 E-mail: 879966473@qq.com
基金资助:
2012年广东省大学生创新训练计划项目(1057312040)

Investigation of the rs28371759 polymorphism of CYP3A4 gene in Guangdong population

WANG Rong, CHEN Ke-rui, LIU Xiao-mei, TANG Hui-en, HE Zhen-yu

Department of Biochemistry and Molecular Biology,Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China

Received:2013-07-22 Revised:2014-11-03 Online:2014-11-26 Published:2014-12-09

摘要/Abstract

摘要： 目的探讨广东人群CYP3A4基因rs28371759(20070T>C)位点的分布特点,为广东患者使用CYP3A4底物药提供理论参考依据。方法以200名广东志愿者的口腔拭子DNA为模板,PCR扩增包含rs28371759多态位点的DNA片断,用限制性内切酶MspI消化PCR产物,通过聚丙烯酰胺凝胶电泳-银染获得样品的限制性酶切图谱用于判别基因型。结果在受检的200例样品中,检出杂合子3例,余者皆为野生型纯合子。野生型纯合子、杂合子、突变型纯合子的频率分别为 0.985、0.015、0,突变等位基因20070C即CYP3A4^*18A的频率为 0.007 5。结论本研究得到了广东人群CYP3A4基因rs28371759 位点的多态性分布情况,为研究CYP3A4

关键词: 广东人群, CYP3A4^*18A, 多态性

Abstract: AIM: To study the genotype distribution of rs28371759(20070T>C) polymorphism of CYP3A4 in Guangdong population and to supply reference information for clinical safe medication of drugs metabolized by CYP3A4. METHODS: Taking 200 Guangdong volunteers' buccal swabs DNA as templates, then the DNA fragments encompassing the rs28371759 polymorphic locus were amplified by polymerase chain reaction,the amplified products were subjected to restriction enzyme analysis with MspI, then the digested products were subjected to polyacrylamide gel electrophoresis and sliver-staining, restriction enzyme maps derived were used for determining the corresponding genotypes.RESULTS: Among these detected 200 samples, heterozygotes were found in 3 cases, while the others were wild-types. The wild homozygotes, heterozygotes, mutant homozygotes were 0.985, 0.015, 0 respectively. The frequency of mutant allele 20070C was 0.0075.CONCLUSION: This research shows distribution of CYP3A4 gene rs28371759 polymorphism locus in Guangdong population, which lay a foundation for researching the relationship between CYP3A4 gene polymorphism and clinical drug effect.

Key words: Guangdong population, CYP3A4^*18A, polymorphism

中图分类号:

R968

王瑢, 陈珂蕊, 刘晓媚, 唐惠恩, 何震宇. 广东人群 CYP3A4基因rs28371759(20070T>C)位点多态性调查[J]. 中国临床药理学与治疗学, 2014, 19(11): 1255-1258.

WANG Rong, CHEN Ke-rui, LIU Xiao-mei, TANG Hui-en, HE Zhen-yu. Investigation of the rs28371759 polymorphism of CYP3A4 gene in Guangdong population[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(11): 1255-1258.

参考文献 12

[1]	陈欣,李玉珍,方翼. CYP3A4代谢药物的特点及其多态性的研究现状[J]. 中国药房, 2010,21(22):2097-2099.
[2]	李赟, 何芳, 曾彩雯,等. CYP2C9、CYP2C19、CYP3A4基因多态性对磺脲类降糖药代谢的影响[J]. 中国临床药理学与治疗学, 2012, 17(5):582-587.
[3]	He BX, Shi L, Qiu J, et al.A functional polymorphism in the CYP3A4 gene is associated with increased risk of coronary heart disease in the Chinese Han population[J]. Basic Clin Pharmacol Toxicol, 2011, 108(3):208-213.
[4]	Maekawa K, Harakawa N, Yoshimura T, et al.CYP3A416 and CYP3A418 alleles found in east asians exhibit differential catalytic activities for seven CYP3A4 substrate drugs[J]. Drug Metab Dispos, 2010, 38(12):2100-2104.
[5]	Tsai SM, Lin CY, Wu SH, et al.Hou.Side effects after docetaxel treatment in Taiwanese breast cancer patients with CYP3A4, CYP3A5, and ABCB1 gene polymorphisms[J]. Clin Chim Acta, 2009, 404(2):160-165.
[6]	李艳梅. 西南地区儿童CYP3A4基因多态性分析与耐药性癫痫相关性研究[D].重庆:重庆医科大学,2012:1-45.
[7]	Lee SJ, Lee SS, Jeong HE, et al.The CYP3A4*18 allele, the most frequent coding variant in asian populations, does not significantly affect the midazolam disposition in heterozygous individuals[J]. Drug Metab Dispos, 2007, 35(11):2095-2101.
[8]	Kang YS,Park SY,Yim CH,et al.The CYP3A4*18 genotype in the cytochrome P450 3A4 gene, a rapid metabolizer of sex steroids, is associated with low bone mineral density[J]. Clin Pharmacol Ther, 2009, 85(3):312-318.
[9]	Dai D, Tang J, Rose R, et al.Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos[J]. J Pharmacol Exp Ther, 2001, 299(3):825-831.
[10]	孙强. 中国维吾尔族人群细胞色素酶CYP450 3A4的遗传多态性探索和分析[D].西安:西北大学,2012:1-63.
[11]	Hu YF, He J, Chen GL, et al.CYP3A53 and CYP3A418 single nucleotide polymorphisms in a Chinese population[J]. Clinica Chimica Acta, 2005, 353(1/2):187-192.
[12]	Hsieh KP, Lin YY, Cheng CL,et al.Novel mutations of CYP3A4 in Chinese[J]. Drug Metab Dispos, 2001, 29(3):268-273.

[1]	李青华, 赵艳, 赵海港, 高朋飞, 徐炳欣. ABCB1 G2677T 基因多态性检测在缺血性脑卒中患者应用阿托伐他汀降脂治疗中的价值[J]. 中国临床药理学与治疗学, 2023, 28(6): 633-640.
[2]	朱丽, 魏兵, 廖世峨, 张超, 郑晓宇, 刘亚军. 药物代谢酶细胞色素P450单核苷酸多态性影响哮喘儿童吸入皮质醇激素疗效研究[J]. 中国临床药理学与治疗学, 2023, 28(5): 536-543.
[3]	石大伟, 郑晓永, 靳晓丹, 赵晓曼, 陈杰, 杜幸军. XPC基因多态性rs2228001对接受卡培他滨为基础辅助化疗的结直肠癌患者预后的影响[J]. 中国临床药理学与治疗学, 2023, 28(4): 391-399.
[4]	周晶, 周琛, 廖珂, 邱爱林, 董巍檑, 郭紫芬. 孕激素受体基因G1978T 多态性与子宫内膜癌的相关性研究[J]. 中国临床药理学与治疗学, 2023, 28(4): 400-406.
[5]	张志英, 靳秀红, 张小宁, 张向峰, 罗青林, 张松林. TBX21和ADCY9多态性在儿童哮喘发生发展中的临床研究[J]. 中国临床药理学与治疗学, 2023, 28(4): 407-412.
[6]	刘璐, 石雨菲, 何庆烽, 徐凤艳, 王鲲, 蔡卫民, 相小强. 群体模型分析方法评估基因多态性对药物PK/PD的影响[J]. 中国临床药理学与治疗学, 2023, 28(11): 1275-1282.
[7]	王爽, 刘嘉, 张月丽. POR*28基因多态性与中国肾移植患者他克莫司稳定剂量的相关性研究[J]. 中国临床药理学与治疗学, 2022, 27(9): 991-997.
[8]	付虹, 田磊. 缺血性脑卒中伴高血压病患者个体化精准治疗的研究[J]. 中国临床药理学与治疗学, 2022, 27(8): 870-876.
[9]	陈文刚, 殷勤, 张巍巍, 周露露, 寇婉青, 袁小龙. 皖南地区高血压患者MTHFR基因多态性分布及与血Hcy相关性研究[J]. 中国临床药理学与治疗学, 2022, 27(7): 768-774.
[10]	武元竹, 刘俊, 杨魁, 彭静, 栾家杰, 韦俊, 张大发, 宋帅, 袁小龙, 王中方, 张年宝, 解丹, 姜鹏, 范洁. 安徽地区汉族人群CYP2C9*3和VKORC1-1639G>A基因多态性分布及对华法林稳定剂量的影响[J]. 中国临床药理学与治疗学, 2022, 27(6): 652-659.
[11]	陈佳音, 王丽, 王立军, 童刚领, 马洁, 陈西敬, 卢杨. 有机阳离子转运体基因多态性与奥沙利铂毒性及疗效的相关性研究[J]. 中国临床药理学与治疗学, 2022, 27(2): 171-177.
[12]	周敏敏, 余露, 韩超, 顾达民, 雷道赟. 人类胆固醇酯转移蛋白rs5882基因多态性与围术期神经认知功能紊乱的相关性[J]. 中国临床药理学与治疗学, 2021, 26(7): 768-774.
[13]	王春玲, 周仁精, 冯瑞, 吴燕能. 脂联素45 T/G基因多态性对利拉鲁肽治疗2型糖尿病患者的临床疗效[J]. 中国临床药理学与治疗学, 2021, 26(3): 312-317.
[14]	李静, 马丽娟, 袁圆, 王捷, 郁长治, 赵军. 吸入性糖皮质激素布地奈德相关基因多态性与哮喘疗效的关系[J]. 中国临床药理学与治疗学, 2021, 26(11): 1250-1258.
[15]	杨春艳, 张文, 王培培, 彭静, 江佳, 宋静, 刘俊, 李越然, 杨魁, 汪盛, 徐振宇, 栾家杰. 叶酸代谢通路相关基因多态性对血清同型半胱氨酸浓度的影响[J]. 中国临床药理学与治疗学, 2021, 26(11): 1259-1264.