SLCO1B1 多态性对塞尔维亚 HIV/AIDS 患者洛匹那韦 C 的影响。
Influence of SLCO1B1 polymorphisms on lopinavir C in Serbian HIV/AIDS patients.
机构信息
Department of Pharmacology, Clinical Pharmacology and Toxicology, School of Medicine, University of Belgrade, Belgrade, Serbia.
Institute for Biomedical Statistics, School of Medicine, University of Belgrade, Belgrade, Serbia.
出版信息
Br J Clin Pharmacol. 2020 Jul;86(7):1289-1295. doi: 10.1111/bcp.14230. Epub 2020 Feb 28.
AIMS
Lopinavir (LPV) is not a first-line regimen. According to recent WHO data, LPV usage in low- and middle-income countries accounted for approximately 52% of the adult and 23% of the paediatric protease inhibitor market in 2017. Since LPV is a substrate for the SLCO1B1 (OATP1B1) transporter, the aim of this study was to assess the impact of SLCO1B1 polymorphisms (rs11045819, rs4149032 and rs4149056) on LPV trough plasma concentrations (C ) in Serbian patients.
METHODS
Plasma samples from 104 HIV/AIDS Caucasians were collected. LPV C was quantified using liquid-chromatography-mass spectrometry. Genotyping was carried out using real-time-PCR-based allelic discrimination. One-way analysis of variance, t test and linear regression were used for data analysis.
RESULTS
The overall mean (SD) LPV C was 5885 ± 2755 ng/mL. Significant differences were between patients with different rs11045819 genotypes: CC (LPV median C = 6072 ng/mL, interquartile range (IQR) = 4318-7617 ng/mL), CA (LPV median C = 4987 ng/mL, IQR = 4300-6295 ng/mL) and AA (LPV median C = 3648 ng/mL, IQR = 1949-4072 ng/mL) (P = .005). Significant differences were also observed according to rs4149032 genotype: CC (LPV median C = 6027 ng/mL, IQR =4548-8250 ng/mL), CT (LPV median C = 5553 ng/mL, IQR = 4300-6888 ng/mL) and TT (LPV median C = 4408 ng/mL, IQR = 3361-5233 ng/mL) (P = .007). For rs4149056 a statistically significant difference between T-homozygotes (LPV median C = 5434 ng/mL, IQR = 3855-6830 ng/mL), heterozygotes (LPV median C = 6707 ng/mL, IQR = 5088-8063 ng/mL) and C-homozygotes (LPV median C = 13906 ng/mL, IQR = 12946-14866 ng/mL) was observed (P = .002). In multivariate regression analysis, only the SLCO1B1 rs4149056 polymorphism was independently associated with higher LPV C (β = 2834.5 [1442-4226.9] ng/mL [P = .001]).
CONCLUSIONS
Our results demonstrate a statistically significant influence of the SLCO1B1 rs4149056 polymorphism on higher LPV C in Caucasian HIV/AIDS patients.
目的
洛匹那韦（LPV）不是一线治疗方案。根据世界卫生组织最近的数据，2017 年 LPV 在中低收入国家的成人和儿科蛋白酶抑制剂市场中分别占约 52%和 23%。由于 LPV 是 SLCO1B1（OATP1B1）转运体的底物，本研究旨在评估 SLCO1B1 多态性（rs11045819、rs4149032 和 rs4149056）对塞尔维亚患者 LPV 谷浓度（C）的影响。
方法
采集了 104 例 HIV/AIDS 高加索人的血浆样本。使用液-质联用技术定量 LPV C。采用实时-PCR 等位基因鉴别法进行基因分型。使用方差分析、t 检验和线性回归进行数据分析。
结果
总体平均（SD）LPV C 为 5885±2755ng/mL。不同 rs11045819 基因型患者间存在显著差异：CC（LPV 中位数 C=6072ng/mL，四分位距（IQR）=4318-7617ng/mL）、CA（LPV 中位数 C=4987ng/mL，IQR=4300-6295ng/mL）和 AA（LPV 中位数 C=3648ng/mL，IQR=1949-4072ng/mL）（P=0.005）。根据 rs4149032 基因型也观察到显著差异：CC（LPV 中位数 C=6027ng/mL，IQR=4548-8250ng/mL）、CT（LPV 中位数 C=5553ng/mL，IQR=4300-6888ng/mL）和 TT（LPV 中位数 C=4408ng/mL，IQR=3361-5233ng/mL）（P=0.007）。对于 rs4149056，T 纯合子（LPV 中位数 C=5434ng/mL，IQR=3855-6830ng/mL）、杂合子（LPV 中位数 C=6707ng/mL，IQR=5088-8063ng/mL）和 C 纯合子（LPV 中位数 C=13906ng/mL，IQR=12946-14866ng/mL）之间存在统计学显著差异（P=0.002）。在多元回归分析中，只有 SLCO1B1 rs4149056 多态性与 LPV C 升高独立相关（β=2834.5[1442-4226.9]ng/mL[P=0.001]）。
结论
我们的研究结果表明，SLCO1B1 rs4149056 多态性对高加索 HIV/AIDS 患者 LPV C 升高有统计学意义的影响。
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