Cytochrome P4502B6 (CYP2B6) G516T influences nevirapine plasma concentrations in HIV-infected patients in Uganda
Cytochrome P4502B6 (CYP2B6) G516T influences nevirapine plasma concentrations in HIV-infected patients in Uganda
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DOI：
10.1111/j.1468-1293.2007.00432.x
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发表时间：
2007-03-01
期刊：
影响因子：
3
通讯作者：
Masur, H.
中科院分区：
文献类型：
--
作者：
Penzak, S. R.;Kabuye, G.;Masur, H.
目的细胞色素P450（CYP 2B 6）基因多态性已被证明影响奈韦拉平在欧洲白人HIV感染者中的血药浓度。尽管奈韦拉平在非洲被广泛使用，但尚未在该人群中评估CYP 2B 6基因型对奈韦拉平暴露的影响。我们旨在确定乌干达坎帕拉HIV感染患者中CYP 2B 6 516位点基因型对奈韦拉平谷浓度的影响。额外的多态性在nevirapine和多药耐药蛋白-1（MDR-1）基因也进行了评估，其影响nevirapineconcentration.Methods以下基因型在所有受试者使用聚合酶链反应-限制性片段长度多态性：CYP 2B 6 G516 T，MDR-1 C3435 T和G2677 T，CYP 3A 4（*）1B和CYP 3A 5（*）3。使用高效液相色谱法测定了23例HIV感染患者的奈韦拉平血浆浓度，这些患者一般健康，服用奈韦拉平200 mg，每日两次，至少14天。采用方差分析和事后检验比较CYP 2B 6基因型组间的奈韦拉平浓度。结果变异等位基因（TT）纯合子个体的奈韦拉平谷浓度中位数为7607 ng/mL，GG和GT个体分别为4181 ng/mL和5559 ng/mL（GG vs TT中位数比值=1.82; P=0.011）。TT与GG个体的平均比值（95%置信区间）为1.51（1.18，1.84）。其他多态性研究和奈韦拉平concentration.Conclusions CYP 2B 6 G516 T显着影响奈韦拉平谷浓度在乌干达的HIV感染患者之间没有观察到关联。需要在更大的患者人群中进行额外的研究，以进一步确定这些初步发现的潜在临床影响。
Objective Polymorphisms in the cytochrome P450 (CYP) 2B6 gene have been shown to influence nevirapine plasma concentrations in HIV-infected European Caucasians. Although nevirapine is used extensively in Africa, the influence of CYP2B6 genotype on nevirapine exposure has not been assessed in this population. We aimed to determine the influence of CYP2B6 genotype at position 516 on nevirapine trough concentrations in HIV-infected patients in Kampala, Uganda. Additional polymorphisms in the CYP and multidrug resistance protein-1 (MDR-1) genes were also assessed for their impact on nevirapine concentrations.Methods The following genotypes were determined in all subjects using polymerase chain reaction-restriction fragment length polymorphism: CYP2B6 G516T, MDR-1 C3435T and G2677T, CYP3A4(*)1B and CYP3A5(*)3. Nevirapine plasma concentrations were determined using high-performance liquid chromatography in 23 HIV-infected patients who were generally healthy and had been taking nevirapine 200 mg twice daily for at least 14 days. Analysis of variance with post hoc testing was used to compare nevirapine concentrations among CYP2B6 genotype groups.Results The median nevirapine trough concentration in individuals homozygous for the variant allele (TT) was 7607 ng/mL vs 4181 and 5559 ng/mL for GG and GT individuals, respectively (GG vs TT median ratio=1.82; P=0.011). The mean ratio for TT vs GG individuals (95% confidence interval) was 1.51 (1.18, 1.84). No associations were observed between the other polymorphisms studied and nevirapine concentrations.Conclusions CYP2B6 G516T significantly influenced nevirapine trough concentrations in HIV-infected patients in Uganda. Additional studies in larger patient populations are necessary to further define the potential clinical impact of these preliminary findings.