title: The Effect of ABCB1 C3435T Polymorphism on Cyclosporine Dose Requirements in Kidney Transplant Recipients: A Meta-Analysis.
abstract: Cyclosporine A (CsA) is a substrate of the multi-drug efflux pump P-glycoprotein (P-gp) encoded by ABCB1. Among the various single nucleotide polymorphisms (SNPs) of ABCB1, C3435T has been extensively investigated to determine the relationship with the pharmacokinetics of CsA. However, the results are controversial. This meta-analysis was designed to evaluate the influence of C3435T SNP on the dose-adjusted trough (C0 /D) and peak (Cmax /D) concentrations of CsA. Based on a literature search of four authoritative databases, 13 studies since 2001 concerning 1293 kidney transplant recipients were included. The results indicated a significant difference of C0 /D and Cmax /D between 3435CC and 3435TT genotype carriers (weighted mean difference (WMD) of C0 /D: 4.18 (ng ml(-1))/(mg kg(-1)), 95% CIs: 1.00-7.37, p = 0.01; WMD of Cmax /D: 20.85 (ng ml(-1))/(mg kg(-1)), 95% CIs: 2.25-39.46, p = 0.03). Subgroup analysis by ethnicity demonstrated that C0 /D was lower in Asian CC versus TT genotype carriers (WMD = 10.32 (ng ml(-1))/(mg kg(-1)), 95% CIs: 4.78-15.85, p = 0.0003) but did not vary by genotype for Caucasian recipients. Moreover, significant variation of C0 /D was found at 1 week and 1-3 months after transplantation between CC and TT genotype carriers. Therefore, this meta-analysis showed a correlation between ABCB1 C3435T polymorphism and the dose-adjusted concentration of CsA. Patients with 3435CC genotype will require a higher dose of CsA to achieve target therapeutic concentrations when compared with 3435TT carriers after kidney transplantation, especially in the Asian population and especially during the early and middle time periods after transplantation.
authors.affiliation: Department of Clinical Pharmacology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, Zhuji City Sixth People's Hospital, Zhuji, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Clinical Pharmacology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Clinical Pharmacology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Linrun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lou
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D044466:Asian People / Q000235:genetics; D016572:Cyclosporine / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D013997:Time Factors; D044465:White People / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D007166:Immunosuppressive Agents; D016572:Cyclosporine