兰州大学机构库 >第二临床医学院
CYP3A5~* 3和CYP3A4~* 18B基因多态性对肾移植患者环孢素药代动力学的影响
Alternative TitleEffect of CYP3A5*3 and CYP3A4*18B genetic polymorphisms on cyclosporine pharmacokinetics in renal transplant patients
胡永芳; 翟所迪; 邱雯
2009-03-20
Source Publication中国药理学通报   Impact Factor & Quartile
ISSN1001-1978
Volume25Issue:3Pages:378-382
Abstract目的回顾性研究肾脏移植后1mon,CYP3A5*3和CYP3A4*18B基因多态性对CsA药代动力学参数的影响。方法采用PCR-RFLP方法分析了63名肾脏移植患者CYP3A5*3和CYP3A4*18B基因型;荧光偏正免疫法用于检测肾移植患者静脉全血中的CsA浓度。结果在63名肾移植患者中,CYP3A5*3和CYP3A4*18B突变等位基因发生频率分别为0.770(95CI:0.767~0.773),0.235(95CI:0.235~0.241),而且这些等位基因表现出完全连锁不平衡。在移植术后1mon内,携带CYP3A4*1/*1野生型纯合子患者的C0以及剂量校正谷血浓度(C0/D)均明显高...
Other AbstractAim To evaluate retrospectively the effect of genetic polymorphisms in CYP3A4 and CYP3A5 on cyclosporine pharmacokinetics during the early period in renal transplant patients. Methods Polymerase chain reaction-restriction fragment length polymorphism was performed to genotype for CYP3A4*18B and CYP3A5*3. Cyclosporine whole blood levels were measured by fluorescence polarization immunoassay. Results The frequencies of CYP3A4*18B and CYP3A5*3 variant alleles were 0. 235 (95 Cl:0. 235 similar to 0.241)and 0.770(95 Cl:0.767 similar to 0.773) respectively in 63 of renal transplantation patients, and these alleles exhibited incomplete linkage disequillbrium. The median ( range) value of cyclosporine dose adjusted blood trough concentrations (C-0/D) and C-0 in CYP3A4*1/*1 genotype patients was higher than that in CYP3A4*1/*18B and CYP3A*18B/*18B patients, the same result was found in CYP3A5 expression (CYP3A5*3/*1 and CYP3A5*1/*3) (P < 0. 05, Mann-Whitney U test); cyclosporine dose in CYP3A5*1/*1 genotype patients were higher than that in CYP3A5*1/*3 or CYP3A5*3/*3 patients (P = 0. 004 < 0. 01, Kruakal-Wallis Test) in the first month after renal transplantation. In addition, no other statistically significant association was found between cyclosporine and CYP3A4*18B as well as CYP3A5*3 SNPs. Conclusions Genetic polymorphism of CYP3A5*3 and CYP3A4*18B may be partly responsible in large interindividual variability of cyclosporine pharmacokinetics after transplantation, but the test for CYP3A5*3 genotype before transplantation remains to be explained.
Keyword单核苷酸多态性 CYP3A5 CYP3A4 环孢素 器官移植
Subject AreaGenetics & Heredity ; Urology & Nephrology
Publication PlaceBEIJING
Indexed ByBIOSIS ; CSCD
Language中文
First Inst
Funding Project国家自然科学基金项目
Host of Journal中国药理学会
Project Number国家自然科学基金资助项目(No30371668)
CSCD IDCSCD:3658680
Funding OrganizationNSFC
SubtypeArticle
BIOSIS IDBIOSIS:PREV200900431387
IRIDCNKI:0038213
Department北京大学第三医院治疗药物监测和临床毒理中心;
兰州大学附属第二医院药剂科
Citation statistics
Cited Times:15[CSCD]   [CSCD Record]
Document Type期刊论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/173449
Collection第二临床医学院
Recommended Citation
GB/T 7714
胡永芳,翟所迪,邱雯. CYP3A5~* 3和CYP3A4~* 18B基因多态性对肾移植患者环孢素药代动力学的影响[J]. 中国药理学通报,2009,25(3):378-382.
APA 胡永芳,翟所迪,&邱雯.(2009).CYP3A5~* 3和CYP3A4~* 18B基因多态性对肾移植患者环孢素药代动力学的影响.中国药理学通报,25(3),378-382.
MLA 胡永芳,et al."CYP3A5~* 3和CYP3A4~* 18B基因多态性对肾移植患者环孢素药代动力学的影响".中国药理学通报 25.3(2009):378-382.
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