Potential implications of CYP3A4, CYP3A5 and MDR-1 genetic variants on the efficacy of Lopinavir/Ritonavir (LPV/r) monotherapy in HIV-1 patients
Potential implications of CYP3A4, CYP3A5 and MDR-1 genetic variants on the efficacy of Lopinavir/Ritonavir (LPV/r) monotherapy in HIV-1 patients
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CYP3A4、CYP3A5 和 MDR-1 基因变异对洛匹那韦/利托那韦 (LPV/r) 单药治疗 HIV-1 患者疗效的潜在影响
DOI：
10.7448/ias.17.4.19589
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发表时间：
2014
影响因子：
6
通讯作者：
R. D'arrigo
中科院分区：
文献类型：
--
作者：
G. Berno;M. Zaccarelli;C. Gori;M. Tempestilli;Luigia Pucci;A. Antinori;C. Perno;Leopoldo Paolo Pucillo;R. D'arrigo
生物转化酶（CYP 3A 4、CYP 3A 5）或转运蛋白（多药耐药MDR 1基因产物，P-gp）中的几种遗传单核苷酸多态性（SNP）参与PI代谢，因此PI药代动力学的特征是个体间变异性较大。本研究的目的是：（i）基于全长CYP 3A 4和CYP 3A 5基因（SNP）和MDR 1 C3435 T变体的DNA纯化，开发内部PCR/直接测序;（ii）研究CYP 3A 4和CYP 3A 5报告或未报告的遗传多态性和MDR 1-C3435 T（CC纯合子、CT杂合子、TT纯合子）与接受PI治疗的HIV-1感染受试者的临床结局的相关性。
Several genetic single nucleotide polymorphisms (SNPs) in biotransformation enzymes (CYP3A4, CYP3A5) or transporter proteins (multidrug resistance MDR1 gene product, P‐gp) are involved in PI metabolism so that PI pharmacokinetics is characterized by a large inter‐individual variability. The aim of this study was: (i) to develop an in‐house PCR/direct sequencing, based on DNA purification of full‐length CYP3A4 and CYP3A5 genes (SNPs) and MDR1 C3435T variant; (ii) to investigate association of CYP3A4 and CYP3A5 reported or unreported genetic polymorphisms and MDR1‐C3435T (CC homozygote, CT heterozygote, TT homozygote) with clinical outcome of HIV‐1 infected subjects treated with PI.