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Effects of the CYP3A5*3 variant on cyclosporine exposure and acute rejection rate in renal transplant patients: a meta-analysis
Tang, Hui-Lin1; Ma, Lu-Lin2; Xie, Hong-Guang3,4; Zhang, Ting1; Hu, Yong-Fang1
关键词cyclosporine CYP3A5 kidney transplantation meta-analysis P-glycoprotein pharmacogenetics pharmacogenomics
刊名PHARMACOGENETICS AND GENOMICS
2010-09-01
DOI10.1097/FPC.0b013e32833ccd56
20期:9页:525-531
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biotechnology & Applied Microbiology ; Genetics & Heredity ; Pharmacology & Pharmacy
研究领域[WOS]Biotechnology & Applied Microbiology ; Genetics & Heredity ; Pharmacology & Pharmacy
关键词[WOS]GENETIC-POLYMORPHISMS ; P-GLYCOPROTEIN ; CALCINEURIN INHIBITORS ; IMMUNOSUPPRESSIVE DRUGS ; KIDNEY-TRANSPLANTATION ; ALLOGRAFT RECIPIENTS ; DOSE REQUIREMENTS ; CYP3A5 EXPRESSION ; BLOOD-PRESSURE ; PHARMACOKINETICS
英文摘要

Background Whether the loss-of-function allele CYP3A5*3 variant is associated with significantly impaired metabolism of cyclosporine A (CsA) in transplant patients is still controversial because of the lack of prospective, large-scale clinical studies performed among diversely ethnic populations.

Objectives This meta-analysis was designed to determine whether the CYP3A5*3 variant could affect CsA blood concentrations and the rate of acute rejection in renal transplant recipients.

Methods and results All relevant publications were retrieved online from 1966 to March 2010, in which 14 studies were chosen, and 1821 renal transplant patients were enrolled. The results showed that there were significant differences in the CsA dose-adjusted trough concentration (C(0)) between the CYP3A5*3/*3 and CYP3A5*1/*1 carriers [weighted mean difference (WMD): 10.06 mu g/l per mg/kg, 95% confidence interval (CI): 3.12-17.00, P = 0.004] and between the non-CYP3A5*1 allele carriers and the CYP3A5*1 allele carriers (WMD: 8.32 mu g/l per mg/kg, 95% CI: 3.16-13.49, P = 0.002). In addition, a subgroup analysis stratified by ethnicity indicated that a significant difference in CsA dose-adjusted C(0) was observed between the non-CYP3A5*1 allele carriers and the CYP3A5*1 allele carriers in Asian patients, but not in Caucasian patients. Moreover, a significant difference in the mean daily dose was observed between the non-CYP3A5*1 allele carriers and the CYP3A5*1 allele carriers (WMD: -0.19 mg/kg, 95% CI: -0.31 to -0.07, P = 0.002). However, the meta-analysis suggested that there was little or no association of the CYP3A5*3 variant with the acute rejection rate in renal transplant patients treated with CsA [odds ratio = 0.94, 95% CI: 0.57-1.54, P = 0.80].

Conclusion We concluded that the CYP3A5*3 variant could be associated, to a certain extent, with increased CsA dose-adjusted C(0) in blood and reduced mean daily doses, but that this genetic variant allele seemed to have little effect on the acute rejection rate in renal transplant patients taking CsA. Pharmacogenetics and Genomics 20: 525-531 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

语种英语
WOS记录号WOS:000281295500001
引用统计
被引频次:20[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62875
专题北京大学第三临床医学院_泌尿外科
北京大学第三临床医学院_眼科
北京大学第三临床医学院_药剂科
作者单位1.Peking Univ, Hosp 3, Dept Urol, Beijing 100191, Peoples R China
2.Univ Calif Washington Ctr, Washington, DC USA
3.Peking Univ, Therapeut Drug Monitoring & Clin Toxicol Ctr, Beijing, Peoples R China
4.Univ Calif San Francisco, Sch Pharm, Ctr Drug Dev Sci, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA
推荐引用方式
GB/T 7714
Tang, Hui-Lin,Ma, Lu-Lin,Xie, Hong-Guang,et al. Effects of the CYP3A5*3 variant on cyclosporine exposure and acute rejection rate in renal transplant patients: a meta-analysis[J]. PHARMACOGENETICS AND GENOMICS,2010,20(9):525-531.
APA Tang, Hui-Lin,Ma, Lu-Lin,Xie, Hong-Guang,Zhang, Ting,&Hu, Yong-Fang.(2010).Effects of the CYP3A5*3 variant on cyclosporine exposure and acute rejection rate in renal transplant patients: a meta-analysis.PHARMACOGENETICS AND GENOMICS,20(9),525-531.
MLA Tang, Hui-Lin,et al."Effects of the CYP3A5*3 variant on cyclosporine exposure and acute rejection rate in renal transplant patients: a meta-analysis".PHARMACOGENETICS AND GENOMICS 20.9(2010):525-531.
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