Parsons Mary, Campa Adriana, Lai Shenghan, Li Yinghui, Martinez Janet Diaz, Murillo Jorge, Greer Pedro, Martinez Sabrina Sales, Baum Marianna K
R. Stempel College of Public Health and Social Work, Florida International University, Miami, FL, USA.
School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
J AIDS Clin Res. 2013 Aug 31;4(9). doi: 10.4172/2155-6113.1000237.
To examine the effects of GSTM1 null-allele polymorphism on oxidative stress and disease progression in HIV infected and HIV/hepatitis C (HCV) co-infected adults.
HIV-infected and HIV/HCV co-infected participants aged 40-60 years old with CD4 cell count >350 cells/ µl, were recruited. GSTM1 genotype was determined by quantitative PCR. Oxidative stress (mitochondrial 8-oxo-2'-deoxyguanosine [8-oxo-dG], malondialdehyde [MDA], oxidized glutathione and Complexes I and IV), apoptosis and HIV disease (CD4 count and viral load) markers were measured. Gene copies were not quantified, thus the Hardy-Weinberg formula was not applicable.
Of the 129 HIV-infected participants, 58 were HIV/HCV co-infected. GSTM1 occurred in 66% (62/94) in those of African descent, and 33% (11/33) of the Caucasians. Those with GSTM1 coding for the functional antioxidant enzyme Glutathione S-transferase (GST), had higher CD4 cell count (β=3.48, p=0.034), lower HIV viral load (β=-0.536, p=0.018), and lower mitochondrial 8-oxo-dG (β=-0.28, p=0.03). ART reduced oxidative stress in the participants with the GSTM1 coding for the functional antioxidant enzyme. HIV/HCV co-infected participants with the GSTM1 coding for the functional antioxidant enzyme also had lower HIV viral load, lower 8-oxo-dG and lower rate of apoptosis, but also higher oxidized glutathione. Alcohol consumption was associated with lower HIV viral load but higher oxidized glutathione in those with the GSTM1 genotype coding for the functional antioxidant enzyme.
The GSTM1 genotype coding for the functional antioxidant enzyme is associated with lower HIV disease severity, and with lower oxidative stress, compared to GSTM1 null-allele polymorphism. HCV co-infection and alcohol use may be associated with increased oxidative stress even in the presence of the GSTM1 coding for the functional antioxidant enzyme. The null-gene, on the contrary, appears to have a detrimental effect on immune function, viral load control, and antioxidant status, suggesting a potential benefit from antioxidants in HIV infected patients with the defective gene.
研究谷胱甘肽硫转移酶M1（GSTM1）无效等位基因多态性对成人HIV感染者及HIV/丙型肝炎病毒（HCV）合并感染者氧化应激及疾病进展的影响。
招募年龄在40至60岁、CD4细胞计数>350个/微升的HIV感染者及HIV/HCV合并感染者。通过定量PCR确定GSTM1基因型。检测氧化应激指标（线粒体8-氧代-2'-脱氧鸟苷[8-氧代-dG]、丙二醛[MDA]、氧化型谷胱甘肽以及复合物I和IV）、凋亡指标以及HIV疾病指标（CD4计数和病毒载量）。未对基因拷贝数进行定量，因此哈迪-温伯格公式不适用。
在129名HIV感染者中，58名同时感染了HCV。非洲裔人群中GSTM1的出现频率为66%（62/94），白种人中为33%（11/33）。携带编码功能性抗氧化酶谷胱甘肽S-转移酶（GST）的GSTM1的患者，CD4细胞计数较高（β=3.48，p=0.034），HIV病毒载量较低（β=-0.536，p=0.018），线粒体8-氧代-dG水平较低（β=-0.28，p=0.03）。抗逆转录病毒治疗（ART）可降低携带编码功能性抗氧化酶的GSTM1的参与者的氧化应激水平。携带编码功能性抗氧化酶的GSTM1的HIV/HCV合并感染者的HIV病毒载量、8-氧代-dG水平及凋亡率也较低，但氧化型谷胱甘肽水平较高。饮酒与携带编码功能性抗氧化酶的GSTM1基因型的患者较低的HIV病毒载量及较高的氧化型谷胱甘肽水平相关。
与GSTM1无效等位基因多态性相比，编码功能性抗氧化酶的GSTM1基因型与较低的HIV疾病严重程度及较低的氧化应激相关。即使存在编码功能性抗氧化酶的GSTM1，HCV合并感染及饮酒也可能与氧化应激增加有关。相反，无效基因似乎对免疫功能、病毒载量控制及抗氧化状态有不利影响，提示对于携带缺陷基因的HIV感染者，抗氧化剂可能具有潜在益处。
