Effect of GSTM1-Polymorphism on Disease Progression and Oxidative Stress in HIV Infection: Modulation by HIV/HCV Co- Infection and Alcohol Consumption

Authors

Mary Parsons, Roberrt Stempel College of Public Health and Social Work, Florida International University
Adriana Campa, Roberrt Stempel College of Public Health and Social Work, Florida International UniversityFollow
Shenghan Lai, School of Medicine, Johns Hopkins University
Yinghui Li, School of Medicine, Johns Hopkins University
Janet Diaz Martinez, Roberrt Stempel College of Public Health and Social Work, Florida International UniversityFollow
Jorge Murillo, Herbert Werheim College of Medicine, Florida International UniversityFollow
Pedro Greer, Herbert Werheim College of Medicine, Florida International UniversityFollow
Sabrina Sales Martinez, Roberrt Stempel College of Public Health and Social Work, Florida International UniversityFollow
Marianna K. Baum, Roberrt Stempel College of Public Health and Social Work, Florida International UniversityFollow

Date of this Version

2013

Document Type

Article

Abstract

Objective—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.

Methods—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.

Results—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.

Conclusion—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 nullgene, 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.

Comments

Copyright: © 2013 Parsons M, et al.

Originally published in the Journal of AIDS & Clinical Research

Identifier

FIDC001535

Recommended Citation

Parsons, Mary; Campa, Adriana; Lai, Shenghan; Li, Yinghui; Diaz Martinez, Janet; Murillo, Jorge; Greer, Pedro; Martinez, Sabrina Sales; and Baum, Marianna K., "Effect of GSTM1-Polymorphism on Disease Progression and Oxidative Stress in HIV Infection: Modulation by HIV/HCV Co- Infection and Alcohol Consumption" (2013). HWCOM Faculty Publications. 31.
https://digitalcommons.fiu.edu/com_facpub/31

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This work is licensed under a Creative Commons Attribution 3.0 License.