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

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 suscept...

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Autores principales: Kuleape, Joshua Agbemefa, Tagoe, Emmanuel Ayitey, Puplampu, Peter, Bonney, Evelyn Yayra, Quaye, Osbourne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967833/
https://www.ncbi.nlm.nih.gov/pubmed/29795558
http://dx.doi.org/10.1371/journal.pone.0195954
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author Kuleape, Joshua Agbemefa
Tagoe, Emmanuel Ayitey
Puplampu, Peter
Bonney, Evelyn Yayra
Quaye, Osbourne
author_facet Kuleape, Joshua Agbemefa
Tagoe, Emmanuel Ayitey
Puplampu, Peter
Bonney, Evelyn Yayra
Quaye, Osbourne
author_sort Kuleape, Joshua Agbemefa
collection PubMed
description 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/mm(3)) was significantly lower than that of patients on ART (604 ± 294 cells/mm(3)), and viral load was significantly lower in the ART-experienced group (30379 ± 15073 copies/mm(3)) compared to the ART-naïve group (209882 ± 75045 copies/mm(3)). 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/mm(3) (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.
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spelling pubmed-59678332018-06-08 Homozygous deletion of both GSTM1 and GSTT1 genes is associated with higher CD4(+) T cell counts in Ghanaian HIV patients Kuleape, Joshua Agbemefa Tagoe, Emmanuel Ayitey Puplampu, Peter Bonney, Evelyn Yayra Quaye, Osbourne PLoS One Research Article 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/mm(3)) was significantly lower than that of patients on ART (604 ± 294 cells/mm(3)), and viral load was significantly lower in the ART-experienced group (30379 ± 15073 copies/mm(3)) compared to the ART-naïve group (209882 ± 75045 copies/mm(3)). 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/mm(3) (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. Public Library of Science 2018-05-24 /pmc/articles/PMC5967833/ /pubmed/29795558 http://dx.doi.org/10.1371/journal.pone.0195954 Text en © 2018 Kuleape et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kuleape, Joshua Agbemefa
Tagoe, Emmanuel Ayitey
Puplampu, Peter
Bonney, Evelyn Yayra
Quaye, Osbourne
Homozygous deletion of both GSTM1 and GSTT1 genes is associated with higher CD4(+) T cell counts in Ghanaian HIV patients
title Homozygous deletion of both GSTM1 and GSTT1 genes is associated with higher CD4(+) T cell counts in Ghanaian HIV patients
title_full Homozygous deletion of both GSTM1 and GSTT1 genes is associated with higher CD4(+) T cell counts in Ghanaian HIV patients
title_fullStr Homozygous deletion of both GSTM1 and GSTT1 genes is associated with higher CD4(+) T cell counts in Ghanaian HIV patients
title_full_unstemmed Homozygous deletion of both GSTM1 and GSTT1 genes is associated with higher CD4(+) T cell counts in Ghanaian HIV patients
title_short Homozygous deletion of both GSTM1 and GSTT1 genes is associated with higher CD4(+) T cell counts in Ghanaian HIV patients
title_sort homozygous deletion of both gstm1 and gstt1 genes is associated with higher cd4(+) t cell counts in ghanaian hiv patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967833/
https://www.ncbi.nlm.nih.gov/pubmed/29795558
http://dx.doi.org/10.1371/journal.pone.0195954
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