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在加纳的 HIV 患者中,GSTM1 和 GSTT1 基因的纯合缺失与较高的 CD4+T 细胞计数相关。

Homozygous deletion of both GSTM1 and GSTT1 genes is associated with higher CD4+ T cell counts in Ghanaian HIV patients.

机构信息

West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Accra, Ghana.

Department of Medicine, Korle Bu Teaching Hospital, Accra, Ghana.

出版信息

PLoS One. 2018 May 24;13(5):e0195954. doi: 10.1371/journal.pone.0195954. eCollection 2018.

Abstract

Glutathione S-transferase (GST) family of enzymes are involved in a two-stage detoxification process of a wide range of environmental toxins, carcinogens and xenobiotics. The GST enzymes play important roles in oxidative stress pathways, and polymorphisms in the GSTM1 and GSTT1 genes mediate susceptibility and outcome in different diseases. Human immunodeficiency virus (HIV) infection is associated with oxidative stress, but there is limited data on the frequency of deleted GSTM1 and GSTT1 genes in HIV/AIDS patients and their effect on progression among Ghanaians. This study sought to investigate the association between homozygous deletion of GSTM1 and GSTT1 genes (both null deletion) with HIV/AIDS disease progression in Ghanaian patients. HIV-infected individuals on antiretroviral therapy (ART), ART-naïve HIV patients, and HIV seronegative individuals were recruited for the study. HIV/AIDS disease progression was assessed by measuring CD4+ cell count and viral load of the patients, and GST polymorphism was determined by amplifying the GSTT1 and GSTM1 genes using multiplex PCR, with CYP1A1 gene as an internal control. The mean CD4+ count of patients that were naïve to ART (298 ± 243 cells/mm3) was significantly lower than that of patients on ART (604 ± 294 cells/mm3), and viral load was significantly lower in the ART-experienced group (30379 ± 15073 copies/mm3) compared to the ART-naïve group (209882 ± 75045 copies/mm3). Frequencies of GSTM1 and GSTT1 deletions were shown to be 21.9% and 19.8%, respectively, in the HIV patients, and patients with homozygous deletion of both GSTM1 and GSTT1 were more likely to have their CD4+ count rising above 350 cells/mm3 (OR = 6.44, 95% CI = 0.81-51.49, p = 0.039) suggesting that patients with homozygous deletion of GSTM1 and GSTT1 genes have slower disease progression. The findings of this study show that double deletion of glutathione S-transferases M1 and T1 is statistically associated with normal CD4+ count in patients diagnosed with HIV/AIDS. Further study is required to investigate the clinical importance of the both null deletion in HIV patients.

摘要

谷胱甘肽 S-转移酶(GST)家族的酶参与广泛的环境毒素、致癌物和异生物的两阶段解毒过程。GST 酶在氧化应激途径中发挥重要作用,GSTM1 和 GSTT1 基因的多态性介导不同疾病的易感性和结果。人类免疫缺陷病毒(HIV)感染与氧化应激有关,但关于 HIV/AIDS 患者中 GSTM1 和 GSTT1 基因缺失的频率及其对加纳人进展的影响的数据有限。本研究旨在探讨加纳 HIV/AIDS 患者中 GSTM1 和 GSTT1 基因(均纯合缺失)缺失与 HIV/AIDS 疾病进展之间的关系。招募接受抗逆转录病毒治疗(ART)的 HIV 感染者、未接受 ART 的 HIV 患者和 HIV 阴性个体进行研究。通过测量患者的 CD4+细胞计数和病毒载量来评估 HIV/AIDS 疾病进展,使用多重 PCR 扩增 GSTT1 和 GSTM1 基因,并以 CYP1A1 基因为内参确定 GST 多态性。未接受 ART 治疗的患者的平均 CD4+计数(298 ± 243 个细胞/mm3)明显低于接受 ART 治疗的患者(604 ± 294 个细胞/mm3),而在有经验的 ART 组中病毒载量明显低于无经验的 ART 组(30379 ± 15073 拷贝/mm3)与无经验的 ART 组相比(209882 ± 75045 拷贝/mm3)。结果显示,HIV 患者中 GSTM1 和 GSTT1 缺失的频率分别为 21.9%和 19.8%,GSTM1 和 GSTT1 纯合缺失的患者更有可能使 CD4+计数上升到 350 个细胞/mm3以上(OR=6.44,95%CI=0.81-51.49,p=0.039),表明 GSTM1 和 GSTT1 基因纯合缺失的患者疾病进展较慢。本研究结果表明,谷胱甘肽 S-转移酶 M1 和 T1 的双重缺失与 HIV/AIDS 患者的正常 CD4+计数具有统计学关联。需要进一步研究以探讨 HIV 患者中两种缺失的临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fe/5967833/5160a5748208/pone.0195954.g001.jpg

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