Glutathione S-Transferase Gene Polymorphism And Antioxidant Enzymes Activity In Hiv/Aids Progression In Ghanaian Patients

Abstract

Glutathione and enzymes such as glutathione S-transferase (GST), glutathione reductase (GR) and superoxide dismutase (SOD) play crucial roles in defending the cell against reactive oxygen species (ROS) which have been implicated in HIV replication. It has been shown that cells infected with HIV generate large amounts of inflammatory products such as superoxide anions, peroxynitrites and other ROS, and is accompanied by the deregulation of antioxidant enzymes. The pro-oxidative stress environment in the cell results in reduction of the protective potential of the antioxidants. GST family of enzymes is involved in a two-stage detoxification process of a wide range of environmental toxins, carcinogens and antiretroviral (ARV) drugs. The GST enzymes play important roles in oxidative stress pathways, and polymorphisms in different GST genes mediate susceptibility and outcome in different diseases. Little information is however known about the polymorphisms in Ghanaian patients. Hence the aim of this study was to investigate GST gene polymorphisms and antioxidant enzymes activities in Ghanaian HIV/AIDS patients. A total of 242 individuals comprising 105 HIV-infected patients on ART, 77 HIV patients who are ART naïve and 60 HIV seronegative people were recruited for the study. The impact of the virus on HIV/AIDS disease progression was assessed by measuring CD4+ cell count and viral load. It was observed that the CD4+ count in the ART naïve patients (298 ± 243 cells/mm3) was significantly less when compared to the HIV patients on ART (604 ± 294 cells/mm3) and control subjects (946 ± 125 cells/mm3). The lower CD4+ count was due to progression of the disease in these individuals. Viral load was significantly lower in the ART patient group (30379 ± 15073 copies/mm3) than the ART naïve group (209882 ± 75045 copies/mm3). The study further investigated the impact of the virus and/or antiretroviral treatment on liver function and hematological profile in the study population. Liver function tests results showed elevated levels of ALP, AST and GGT in both HIV patient groups which suggest liver toxicity. Liver toxicity in these patients could be due to the virus in ART naïve patients whereas in those on treatment, it could be due to the antiretroviral drugs. Haematological profile results showed that the ART naïve individuals had normal RBC count of [4.0 ± 0.8 (1012 /L)], but low hemoglobin (10.8 ± 2.2 g/dL) as well as low hematocrit (32.7 ± 6.1 %) and mean corpuscular volume levels (81.2 ± 8.5 fL) compared to ART treatment patients and the seronegative control group. Hence, the ART naïve patients could be suffering from iron-deficiency anemia. The results from the liver function and hematological profile suggest a possible ineffective clearance of ROS. In confirmation of the proposed ineffective clearance of ROS, activities of superoxide dismutase (SOD) and glutathione reductase (GR), and the levels of reduced glutathione (GSH) were investigated. Significantly low SOD and GR activities, as well as GSH levels were observed in the ART naive patients and those with CD4 count below 200 cells/mm3. More importantly, this study is the first report of the frequencies of GSTM1 and GSTT1 deletions in Ghana which were shown to be 21.9% and 19.8%, respectively in HIV patients and those who had a homozygous deletion of both GSTM1 and GSTT1 were at risk of their CD4 count falling below 350 cells/mm3.