Olagunju Adeniyi, Siccardi Marco, Amara Alieu, Jevtovic Djordje, Kusic Jovana, Owen Andrew, Dragovic Gordana
*Department of Molecular and Clinical Pharmacology, University of Liverpool, United Kingdom; †Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria; ‡Infectious and Tropical Diseases Hospital, School of Medicine; and §Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Serbia.
Ther Drug Monit. 2014 Dec;36(6):734-8. doi: 10.1097/FTD.0000000000000098.
Genetic factors have been associated with efavirenz (EFV) plasma concentrations in different populations. In this study, we investigated the effects of CYP2B6 516G>T (rs3745274), CYP2B6 c.485-18C>T (rs4803419), CAR c.540C>T (rs2307424), CAR c.152-1089T>C (rs3003596), and smoking status in a cohort of Serbian patients with HIV.
Patients with HIV positive, all whites, were recruited from the HIV/AIDS Center at the Infectious and Tropical Diseases Hospital, University of Belgrade Teaching Hospital, Belgrade, Serbia. Mid dose (10-14 hours after dose) EFV plasma concentration was determined using a validated liquid chromatography/tandem mass spectrometry method. Genotyping for CYP2B6 516G>T (rs3745274), CYP2B6 c.485-18C>T (rs4803419), CAR c.540C>T (rs2307424), and CAR c.152-1089T>C (rs3003596) was conducted using allelic discrimination real-time polymerase chain reaction assay. One-way analysis of variance, Mann-Whitney test, Pearson or Spearman correlation, and multiple linear regression were used for data analysis.
Minor allele frequencies were similar to frequencies reported in other European populations. The overall mean (95% confidence interval) plasma EFV concentration was 2800 ng/mL (2460-3140). Significant differences between patients based on CYP2B6 516G>T (rs3745274) genotypes were observed: GG (n = 60), 2320 (range, 2160-2480) ng/mL; GT (n = 30), 3230 (range, 2790-3670) ng/mL; and TT (n = 2), 10,700 (range, 6170-15,300) ng/mL (P = 2.0 × 10). In multivariate linear regression analysis, CYP2B6 516G>T (rs3745274) [β = 1770 (1230 to 2310) ng/mL, P < 0.0001] and smoking status [β = -464 (-1250 to -43.3) ng/mL, P = 0.038] were independently associated with plasma EFV concentrations.
The effects of CYP2B6 516G>T (rs3745274) and smoking status on EFV plasma concentration in the Serbian population have been established for the first time.
在不同人群中，遗传因素与依非韦伦（EFV）的血浆浓度有关。在本研究中，我们调查了CYP2B6 516G>T（rs3745274）、CYP2B6 c.485-18C>T（rs4803419）、CAR c.540C>T（rs2307424）、CAR c.152-1089T>C（rs3003596）以及吸烟状况对一组塞尔维亚HIV患者的影响。
HIV阳性患者，均为白人，从塞尔维亚贝尔格莱德大学教学医院传染病与热带病医院的HIV/AIDS中心招募。使用经过验证的液相色谱/串联质谱法测定中剂量（给药后10 - 14小时）的EFV血浆浓度。采用等位基因鉴别实时聚合酶链反应法对CYP2B6 516G>T（rs3745274）、CYP2B6 c.485-18C>T（rs4803419）、CAR c.540C>T（rs2307424）和CAR c.152-1089T>C（rs3003596）进行基因分型。采用单因素方差分析、曼 - 惠特尼检验、Pearson或Spearman相关性分析以及多元线性回归进行数据分析。
次要等位基因频率与其他欧洲人群报道的频率相似。EFV血浆浓度的总体均值（95%置信区间）为2800 ng/mL（2460 - 3140）。观察到基于CYP2B6 516G>T（rs3745274）基因型的患者之间存在显著差异：GG（n = 60），2320（范围，2160 - 2480）ng/mL；GT（n = 30），3230（范围，2790 - 3670）ng/mL；TT（n = 2），10700（范围，6170 - 15300）ng/mL（P = 2.0×10）。在多元线性回归分析中，CYP2B6 516G>T（rs3745274）[β = 1770（1230至2310）ng/mL，P < 0.0001]和吸烟状况[β = -464（-1250至-43.3）ng/mL，P = 0.038]与血浆EFV浓度独立相关。
首次确定了CYP2B6 516G>T（rs3745274）和吸烟状况对塞尔维亚人群中EFV血浆浓度的影响。
