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在接受依非韦伦治疗的HIV感染患者中,ABCB1 3435C>T和CYP2B6 516G>T与高密度脂蛋白胆固醇的关系。

The relationships of ABCB1 3435C>T and CYP2B6 516G>T with high-density lipoprotein cholesterol in HIV-infected patients receiving Efavirenz.

作者信息

Mahungu T W, Nair D, Smith C J, Egan D, Youle M, Johnson M A, Khoo S H, Back D J, Owen A

机构信息

Department of HIV Medicine, Royal Free NHS Trust, London, UK.

出版信息

Clin Pharmacol Ther. 2009 Aug;86(2):204-11. doi: 10.1038/clpt.2009.78. Epub 2009 May 27.

Abstract

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are associated with a favorable increase in high-density lipoprotein cholesterol (HDL-c) level. Isolated studies have found a direct correlation between efavirenz (EFV) exposure and HDL-c level changes. Here we explore the impact that drug disposition variants associated with EFV exposure have on changes in HDL-c level. Seventy-six patients on first-line EFV-based regimens were genotyped for CYP2B6 516G>T and ABCB1 3435C>T. There was a 37% increase (+0.32 mmol/l, P < 0.001) in mean HDL-c level over 48 weeks, and this was univariately associated with gender (male +0.26 mmol/l, female +0.55 mmol/l; P = 0.03), ABCB1 3435C>T (CC +0.26 mmol/l, CT +0.16 mmol/l, TT +0.54 mmol/l; P(ANOVA) = 0.003) and CYP2B6 516 G>T (GG +0.27 mmol/l, GT +0.29 mmol/l, TT +0.72 mmol/l; P(ANOVA) = 0.08). There was a significant association between the cumulative number of predictive genotypes (CYP2B6 516TT or ABCB1 3435TT) and mean HDL-c level change: (group 0 +0.20 mmol/l, group 1 +0.47 mmol/l, group 2 +1.00 mmol/l; P(ANOVA) < 0.0001). These findings need to be validated in independent cohorts.

摘要

非核苷类逆转录酶抑制剂(NNRTIs)与高密度脂蛋白胆固醇(HDL-c)水平的有利升高有关。个别研究发现依非韦伦(EFV)暴露与HDL-c水平变化之间存在直接关联。在此,我们探讨与EFV暴露相关的药物处置变异对HDL-c水平变化的影响。对76例接受基于EFV的一线治疗方案的患者进行CYP2B6 516G>T和ABCB1 3435C>T基因分型。在48周内,平均HDL-c水平升高了37%(+0.32 mmol/l,P < 0.001),单因素分析显示这与性别(男性+0.26 mmol/l,女性+0.55 mmol/l;P = 0.03)、ABCB1 3435C>T(CC +0.26 mmol/l,CT +0.16 mmol/l,TT +0.54 mmol/l;P(方差分析)= 0.003)和CYP2B6 516 G>T(GG +0.27 mmol/l,GT +0.29 mmol/l,TT +0.72 mmol/l;P(方差分析)= 0.08)有关。预测基因型(CYP2B6 516TT或ABCB1 3435TT)的累积数量与平均HDL-c水平变化之间存在显著关联:(0组+0.20 mmol/l,1组+0.47 mmol/l,2组+1.00 mmol/l;P(方差分析)< 0.0001)。这些发现需要在独立队列中进行验证。

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