MDR1 C3435T基因多态性对环孢素体内代谢影响的荟萃分析

目的 过荟萃分析进一步观察MDR1 3435T 基因多态性对于环孢素体内代谢的影响。方法 过Pubmed搜索C3435T基因多态性对于环孢素体内代谢影响的相关文献，提取AUC0-4，AUC0-12，AUC0-inf,Cmax,CL/F,和C0等药物动力学参数，使用STATA9.1软件进行荟萃分析。结果 共有14篇参考文献，包括1036名受试者符合本次荟萃分析的入选争件，荟萃分析显示在C3435T野生型杂合子（CC）中，AUC0-12低于其他基因型的受试者。在白种人中，C3435T野生型杂合子（CC）携带者的C0低于其他基因型的白种受试者。其他药物动力学参数在C3435T各基因型之间未见显著差异。结论本荟萃分析没有发现MDR1 C3435T基因多态性对于环孢素体内代谢有较大的影响，但是观察指标的选择是观察结果差异的原因之一；MDR1 C3435T表型和基因型的相关性可能存在种族差异．

Meta-analysis of the effect of MDR1 C3435T polymorphism on cyclosporine pharmacokinetics

Objective To conduct a meta-analysis of significant magnitude to investigate the influence of SNP C3435T on the pharmacokinetics of cyclosporine. Methods Literatures were searched to locate relevant papers by using PubMed electronic sources from 1997 onwards. The pharmacokinetic parameters including AUC0-4, AUC0-12, AUC0-inf, Cmax, CL/F, and Co were extracted and meta-analysis was performed using STATA 9.1. Results A total of 14 papers concerning 1036 subjects were included in this meta-analysis. The over-all results showed no major influence of SNP C3435T on the pharmacokinetic parameters including AUC0-4, AUCu-inf, CL/F, Cmax, and trough concentration （G0）, though AUC0-12 was lower in the subjects with CC genotype. Sub-analysis by ethnic population showed Co was lower in Caucasian subjects harboring CC genotype. Conclusion Our meta-analysis of available studies has failed to demonstrate a definitive correlation between the SNP C3435T in MDR1 gene and alterations in P-gp function that can result in altered pharmacokinetics of cyclosporine, though 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 AUCo-12 than those with at least one T allele. There seems to be ethnic difference in the relationship between the SNP C3435T of MDR1 and eyelospo- rine pharmacokinetics.