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南非 HIV-1 感染患者中 MDR1 C3435T 和 CYP2B6 G516T 多态性的流行率。

Prevalence of MDR1 C3435T and CYP2B6 G516T polymorphisms among HIV-1 infected South African patients.

机构信息

AIDS Virus Research Laboratory, Department of Microbiology, University of Venda, Thohoyandou, South Africa.

出版信息

Dis Markers. 2012;32(1):43-50. doi: 10.3233/DMA-2012-0859.

DOI:10.3233/DMA-2012-0859
PMID:22297601
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3826384/
Abstract

Data on genetic polymorphisms associated with response to anti-HIV drugs has accumulated over the years. Information on how polymorphisms influence drug metabolism and transport to target sites is important in guiding dosage or selection of appropriate alternative therapies. This study determined the frequency of MDR1 C3435T and CYP2B6 G516T polymorphisms associated with the transport and metabolism of efavirenz and nevirapine, in a population of South African HIV infected patients. In addition, association of polymorphisms with immunologic and virologic factors was investigated. A 207bp of MDR1 exon 26 and a 161bp of CYP2B6 exon 4 were obtained from patients by polymerase chain reaction. Analysis of population-based sequences of MDR1 revealed a frequency of 89% and 11% of C and T alleles respectively (n=197; X^{2} = 0.974; p=0.324). Restriction fragment length polymorphism (RFLP) analysis of the CYP2B6 gene revealed a prevalence of 9.5% of GG, 78.4% of GT and 12.1% of TT genotype (n= 199; X^{2} = 65.204; p=0.00). There was no significant difference between immune recovery and decline in viral load (n=53), with genotype after repeated calculations of analysis of variance (ANOVA).

摘要

多年来,与抗 HIV 药物反应相关的遗传多态性数据不断积累。关于多态性如何影响药物代谢和向靶部位转运的信息,对于指导剂量或选择适当的替代治疗方法非常重要。本研究旨在确定与依非韦伦和奈韦拉平转运和代谢相关的 MDR1 C3435T 和 CYP2B6 G516T 多态性在南非 HIV 感染患者人群中的频率。此外,还研究了多态性与免疫和病毒学因素的相关性。通过聚合酶链反应从患者中获得 MDR1 外显子 26 的 207bp 和 CYP2B6 外显子 4 的 161bp。对 MDR1 基于人群的序列进行分析,发现 C 和 T 等位基因的频率分别为 89%和 11%(n=197;X2=0.974;p=0.324)。CYP2B6 基因的限制性片段长度多态性(RFLP)分析显示 GG 基因型的患病率为 9.5%,GT 基因型的患病率为 78.4%,TT 基因型的患病率为 12.1%(n=199;X2=65.204;p=0.00)。在病毒载量免疫恢复和下降之间(n=53),经过方差分析(ANOVA)的重复计算后,基因型没有显著差异。

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