Mpeta Bafokeng, Kampira Elizabeth, Castel Sandra, Mpye Keleabetswe L, Soko Nyarai D, Wiesner Lubbe, Smith Peter, Skelton Michelle, Lacerda Miguel, Dandara Collet
Division of Human Genetics, Department of Pathology (formerly Clinical Laboratory Sciences) & Institute of Infectious Disease & Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.
Malawi College of Health Sciences, University of Malawi, Blantyre, Malawi.
Pharmacogenomics. 2016 May;17(7):679-90. doi: 10.2217/pgs.16.14. Epub 2016 May 4.
Variability in lopinavir (LPV) plasma concentration among patients could be due to genetic polymorphisms. This study set to evaluate significance of variants in CYP3A4/5, SLCO1B1 and ABCC2 on LPV plasma concentration among African HIV-positive patients.
MATERIALS & METHODS: Eighty-six HIV-positive participants on ritonavir (LPV/r) were genetically characterized and LPV plasma concentration determined.
RESULTS & DISCUSSION: LPV plasma concentrations differed >188-fold (range 0.0206-38.6 µg/ml). Both CYP3A422 and SLCO1B1 rs4149056G (c.521C) were not observed in this cohort. CYP3A41B, CYP3A53, CYP3A56 and ABCC2 c.1249G>A which have been associated with LPV plasma concentration, showed no significant association.
These findings highlight the need to include African groups in genomics research to identify variants of pharmacogenomics significance.
患者中洛匹那韦（LPV）血浆浓度的变异性可能归因于基因多态性。本研究旨在评估细胞色素P450 3A4/5（CYP3A4/5）、有机阴离子转运多肽1B1（SLCO1B1）和ATP结合盒转运体C2（ABCC2）基因变异对非洲HIV阳性患者LPV血浆浓度的影响。
对86名接受利托那韦（LPV/r）治疗的HIV阳性参与者进行基因分型，并测定其LPV血浆浓度。
LPV血浆浓度差异超过188倍（范围为0.0206 - 38.6μg/ml）。本队列中未观察到CYP3A422和SLCO1B1 rs4149056G（c.521C）。与LPV血浆浓度相关的CYP3A41B、CYP3A53、CYP3A56和ABCC2 c.1249G>A未显示出显著关联。
这些发现凸显了在基因组学研究中纳入非洲人群以鉴定具有药物基因组学意义的变异的必要性。
Zotero 插件