CYP2B6 genotype is a strong predictor of systemic exposure to efavirenz in HIV-infected Zimbabweans
CYP2B6 genotype is a strong predictor of systemic exposure to efavirenz in HIV-infected Zimbabweans
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DOI：
10.1007/s00228-011-1118-0
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发表时间：
2012-03-01
影响因子：
2.9
通讯作者：
Nakamura, Yusuke
中科院分区：
文献类型：
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作者：
Maimbo, Milimo;Kiyotani, Kazuma;Nakamura, Yusuke
目的抗逆转录病毒药物依法韦仑主要经细胞色素P450 2B 6（CYP 2B 6）、尿苷二磷酸葡萄糖醛酸转移酶2B 7（UGT 2B 7）和CYP 2A 6代谢。在这项研究中，我们调查了单核苷酸多态性（SNP）在这些基因与血浆efavirenz水平在津巴布韦的人类免疫缺陷病毒（HIV）阳性患者efavirenz.Methods治疗的CYP 2B 6，CYP 2A 6，和UGT 2B 7基因的外显子区域进行了重新测序，在49名艾滋病毒感染的津巴布韦患者接受联合治疗，包括efavirenz。在这三个基因的SNPs与依法韦仑血浆浓度11-16小时后，管理的treatment.Results八例携带CYP 2B 6 *6/*18显示出最高的血浆依法韦仑水平，与一个四倍高的浓度比携带CYP 2B 6 *1/*1的患者进行了评估。CYP 2B 6 *6/*6患者的依法韦仑血浆浓度也高于CYP 2B 6 *1/*1患者。在CYP 2A 6和UGT 2B 7分别检测到的17个和12个SNP中，没有SNP与依法韦仑的血药浓度显著相关。结论虽然仅基于有限的受试者，但我们的研究结果表明，CYP 2B 6 *6和CYP 2B 6 *18等位基因可能影响肝脏代谢活性并提高依法韦仑的体循环水平。这可能导致津巴布韦艾滋病患者中毒。
Objective Efavirenz, an antiretroviral medicine, is extensively metabolized by cytochrome P450 2B6 (CYP2B6), UDP-glucuronosyltransferase 2B7 (UGT2B7), and CYP2A6. In this study, we investigated the association of single nucleotide polymorphisms (SNPs) in these genes with plasma efavirenz levels in Zimbabwean human immunodeficiency virus (HIV)-positive patients treated with efavirenz.Methods The exon regions of the CYP2B6, CYP2A6, and UGT2B7 genes were re-sequenced in 49 HIV-infected Zimbabwean patients treated with a combination therapy including efavirenz. Associations of SNPs in these three genes with efavirenz plasma concentrations 11-16 h after the administration of treatment were evaluated.Results Eight patients carrying CYP2B6*6/*18 showed the highest plasma efavirenz levels, with a fourfold higher concentration than patients who carried CYP2B6*1/*1. Patients with CYP2B6*6/*6 also showed higher efavirenz plasma concentrations than those with CYP2B6*1/*1. Among the 17 and 12 SNPs identified in CYP2A6 and UGT2B7, respectively, no SNP showed a significant association with the plasma efavirenz concentration.Conclusion Although based on only a limited number of subjects, our results suggest that the CYP2B6*6 and CYP2B6*18 alleles should affect hepatic metabolic activity and elevate the systemic circulation level of efavirenz, which may lead to toxicity in Zimbabwean HIV patients.