Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University.
Drug Metab Pharmacokinet. 2013;28(5):391-7. doi: 10.2133/dmpk.dmpk-12-rg-120. Epub 2013 Feb 12.
Efavirenz is mainly metabolized by cytochrome P450 2B6 (CYP2B6). This study aimed to examine the frequencies of CYP2B6 and the association between CYP2B6 polymorphisms and plasma efavirenz concentrations in an HIV-1 infected Thai population. Mid-dose plasma efavirenz concentration was determined at 12 weeks following the initiation of an antiretroviral therapy (tenofovir, lamivudine and efavirenz) in 100 Thai adults with HIV-1 infection using high-performance liquid chromatography. Candidate CYP2B6 polymorphisms (c.64C>T, c.499C>G, c.516G>T, c.785A>G, c.1375A>G, c.1459C>T) were conducted by real-time PCR-based allelic discrimination. The most frequent polymorphisms among this cohort were the CYP2B6 c.785A>G and c.516G>T, which had a frequency of 0.36 and 0.32, respectively. From the cases observed, two single nucleotide polymorphisms (SNPs) (c.516G>T and c.785A>G) were significantly associated with high efavirenz plasma levels (p < 0.05). The most frequent haplotypic combinations were *1/*6, *1/*1, *1/*2 and *6/*6 at a frequency of 42.0%, 32.0%, 8.0% and 7.0%, respectively. Increased plasma concentrations of efavirenz were present in individuals with CYP2B6 *6/6 [7.210 mg/L; interquartile range (IQR), 5.020-9.260] when compared to those with CYP2B61/*1 (1.570 mg/L; IQR, 1.295-2.670), p < 0.001. In our study, the impact of SNPs which are correlated with a high level of efavirenz plasma concentrations was found. The genetic configuration of SNPs which are associated with high plasma efavirenz levels may be useful in optimizing the efavirenz dose that is used in HIV-1 infected patients.
依非韦伦主要通过细胞色素 P450 2B6（CYP2B6）代谢。本研究旨在探讨细胞色素 P450 2B6（CYP2B6）的频率以及 CYP2B6 多态性与泰国 HIV-1 感染者血浆依非韦伦浓度之间的相关性。100 例 HIV-1 感染者在开始抗病毒治疗（替诺福韦、拉米夫定和依非韦伦）12 周后，采用高效液相色谱法测定中剂量血浆依非韦伦浓度。采用基于实时 PCR 的等位基因鉴别法检测候选 CYP2B6 多态性（c.64C>T、c.499C>G、c.516G>T、c.785A>G、c.1375A>G、c.1459C>T）。该队列中最常见的多态性是 CYP2B6 c.785A>G 和 c.516G>T，其频率分别为 0.36 和 0.32。从观察到的病例中，两个单核苷酸多态性（SNPs）（c.516G>T 和 c.785A>G）与依非韦伦的高血浆水平显著相关（p<0.05）。最常见的单倍型组合是*1/*6、*1/*1、*1/2 和6/6，频率分别为 42.0%、32.0%、8.0%和 7.0%。与 CYP2B61/1 相比，CYP2B66/*6 个体的依非韦伦血浆浓度升高[7.210 mg/L；四分位间距（IQR），5.020-9.260]（p<0.001）。在我们的研究中，发现了与依非韦伦血浆浓度高相关的 SNP 的影响。与高血浆依非韦伦水平相关的 SNP 的遗传结构可能有助于优化用于 HIV-1 感染者的依非韦伦剂量。
