title: Meta-analysis of the effect of MDR1 C3435T polymorphism on cyclosporine pharmacokinetics.
abstract: The published data revealed conflicting results of the polymorphism of MDR1 exon 26 SNP C3435T on the pharmacokinetics of cyclosporine; thus, the aim was to conduct a meta-analysis of significant magnitude to investigate the influence of SNP C3435T on the pharmacokinetics of cyclosporine. A literature search was conducted to locate the relevant papers by using the PubMed electronic source from 1997 and onwards. The pharmacokinetic parameters, including AUC(0-4), AUC(0-12), AUC(0-inf), C(max), CL/F and trough concentration (C(0)), were extracted and a meta-analysis was performed by using Stata version 9.1. A total of 14 papers concerning 1036 individuals were included in the meta-analysis. The overall results showed no major influence of SNP C3435T on the pharmacokinetic parameters, including AUC(0-4), AUC(0-inf), CL/F, C(max) and C(0), although AUC(0-12) was lower in subjects with CC genotype. A subanalysis by ethnic population showed that C(0) was lower in Caucasian individuals harbouring CC genotype. In conclusion, our meta-analysis of available studies has thus far failed to demonstrate a definitive correlation between the SNP C3435T in MDR1 gene and alterations in P-glycoprotein function that can result in altered pharmacokinetics of cyclosporine, although it was indicated in this meta-analysis that the carrier of CC genotype of the SNP C3435T of MDR1 had lower cyclosporine exposure presented as AUC(0-12) than those with at least one T allele. There seems to be ethnic differences in the relationship between the SNP C3435T of MDR1 and cyclosporine pharmacokinetics.
authors.affiliation: Laboratory of Clinical Pharmacology, Department of Hematology, Xiang-Ya Hospital, Central-South University, Changsha, China.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Jiang
authors.forename: Yi-Ren
authors.initials: YR
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Liu
authors.forename: Xie-Lan
authors.initials: XL
authors.lastname: Zhao
authors.forename: Fang-Ping
authors.initials: FP
authors.lastname: Chen
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000483:Alleles; D019540:Area Under Curve; D016572:Cyclosporine / Q000493:pharmacokinetics*; D005091:Exons; D019450:Genes, MDR; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016572:Cyclosporine