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CYP3A4*1G和3A5*3基因多态性对肾移植患者地尔硫?浓度/剂量比的影响
  • ISSN号:1001-6821
  • 期刊名称:《中国临床药理学杂志》
  • 时间:0
  • 分类:R974.2[医药卫生—药品;医药卫生—药学]
  • 作者机构:[1]湘潭市中心医院科教科,湖南湘潭411100, [2]中南大学湘雅三医院药学部,长沙410033, [3]衡阳市中心医院药剂科,湖南衡阳421000, [4]中南大学湘雅三医院移植科,长沙410033
  • 相关基金:国家自然科学基金资助项目(81102512,81273594);教育部博士点基金资助项目(20110162120023);新世纪优秀人才支持计划基金资助项目(NCET-13-0605);湖南省自然科学基金资助项目(14JJ7001)
中文摘要:

目的:研究肾移植患者中CYP3A4*1G和CYP3A5*3基因多态性对地尔硫?浓度/剂量比的影响。方法以47例肾移植患者为研究对象,用聚合酶链式反应-限制性内切片段长度多态性方法测定肾移植患者药物代谢酶基因型,用高效液相色谱法测定地尔硫?的血药浓度谷值,比较CYP3A4*1G和CYP3A5*3基因多态性对肾移植患者地尔硫?浓度/剂量比的影响。结果 CYP3 A4*1*1型14例(29.79%)、CYP3A4*1*1G型26例(55.32%),CYP3A4*1G*1G型7例(14.89%),G等位基因分布频率为57.45%,A等位基因分布频率为42.55%;CYP3A5*1*1型6例(12.77%), CYP3A5*1*3型21例(44.68%), CYP3A5*3*3型20例(42.55%),G等位基因分布频率为64.89%,A等位基因分布频率为35.11%。肾移植患者中CYP3A4*1G基因多态性对地尔硫?浓度/剂量比有显著影响,CYP3A4*1*1型受者比携带CYP3A4*1G等位基因肾移植患者的浓度/剂量比高1.52倍,差异有统计学意义( P<0.05);而CYP3A5*3基因多态性对浓度/剂量比影响较轻微,且差异无统计学意义。结论肾移植患者中CYP3A4*1G基因多态性对地尔硫?浓度/剂量比有显著影响。

英文摘要:

Objective To investigate the impact of the CYP3A4*1G and CYP3 A5*3 polymorphisms on the concentration/dose ratios of dilti-azem in kidney transplant patients.Methods Forty -seven cases of kidney transplant recipients were recruited.CYP3A4 and CYP3A5 geno-types were determined by polymerase chain reaction -restriction fragment length polymorphism.Plasma trough concentration of diltiazem was meas-ured by HPLC.The effects of CYP3A4*1G and CYP3A5*3 gene poly-morphisms on the concentration/dose ratios of diltiazem were evaluated and compared.Results There were fourteen cases of CYP3A4*1*1 (29.79%) homozygous genotype , twenty six cases of CYP3A4*1*1G (55.32%) heterozygous genotype , and seven cases of CYP3A4*1G*1G (14.89%) homozygous genotype.Allele frequencies of CYP3A4*1 and *1G were 57.45%and 42.55%, respectively.There were six ca-ses with CYP3A5*1*1 (12.77%), twenty one cases with CYP3A5*1*3(44.68%), and twenty cases with CYP3A5*3*3(42.55%).Allele frequencies of CYP3A5*1 and *3 were 35.11%and 64.89%, respectively.CYP3A4*1G gene polymorphisms were significantly related to the concentration /dose of diltiazem in kidney transplant patients.The diltiazem blood trough concentration/dose in CYP3A4*1*1 recipients was 1.52 times higher than that in patients with CYP 3A4*1G allelic genes.There was significant difference in diltiazem blood trough concen-tration/dose ratios between recipients with CYP3A4*1*1 genotypes and CYP3A4*1G carriers(P<0.05).CYP3A5*3 gene polymorphisms had slight impacts on diltiazem blood trough concentration /dose ratios but no difference was found among the CYP3A5 genotypes.Conclusion The CYP3A4*1G gene polymorphism is closely related to the blood con-centration/dose ratios of diltiazem in kidney transplant patients.

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期刊信息
  • 《中国临床药理学杂志》
  • 北大核心期刊(2011版)
  • 主管单位:中国科学技术协会
  • 主办单位:中国药学会
  • 主编:韩启德
  • 地址:北京市海淀区学院路38号
  • 邮编:100191
  • 邮箱:cjcp1985@163.com
  • 电话:010-82802540
  • 国际标准刊号:ISSN:1001-6821
  • 国内统一刊号:ISSN:11-2220/R
  • 邮发代号:82-142
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),美国剑桥科学文摘,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:22227