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  

Effect of CYP3A4* 1G /3A5* 3 gene polymorphism on concentration /dose ratios of diltiazem in kidney transplant patients

作　　者：易鑫 汪江林[2] 周亚男 陈清洁[2] 成柯[4] 明英姿[4] 马颖[4] 左笑丛[2] 

机构地区：[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

出　　处：《中国临床药理学杂志》2014年第8期667-670,共4页The Chinese Journal of Clinical Pharmacology

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)

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 CYP3A4*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。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%,＆amp;nbsp;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＆lt;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.

关 键 词：地尔硫革 细胞色素P450 3A4＊1G 细胞色素P450 3A5＊3 基因多态性 肾移植 

分 类 号：R974.2[医药卫生—药品]