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Impact of GSTM1, GSTT1 and GSTP1 gene polymorphism and risk of ARV-associated hepatotoxicity in HIV-infected individuals and its modulation

The Pharmacogenomics Journal volume 17, pages 53–60 (2017)Cite this article

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Abstract

Glutathione S-transferase (GST) family is involved in a two-stage detoxification process of a wide range of environmental toxins, carcinogen and antiretroviral (ARV) therapy (ART) drugs. The aim of this study is to describe the impact of genetic polymorphisms of GSTM1, GSTT1 and GSTP1-313A/G in the risk of ARV-associated hepatotoxicity in HIV-infected individuals and its modulation in hepatotoxic patients. We enrolled a total of 34 patients with hepatotoxicity, 131 HIV-infected individuals without hepatotoxicity under non-nucleoside reverse transcriptase inhibitor containing ART and 153 unrelated healthy individuals. With a case–control design, polymorphisms of GSTM1, GSTT1 and GSTP1-313A/G gene were genotyped by PCR and restriction enzyme-length polymorphism. Genotypes of GSTT1 null were significantly higher in HIV-infected individuals as compared with healthy controls (P=0.01, odds ratio (OR)=1.54). HIV-infected individuals with GSTM1-null genotype showed higher risk (P=0.09, OR=1.37) for hepatotoxicity, but risk was not significant. On evaluating gene–gene interaction models, GSTM1 null and GSTT1 null showed significant association with the risk of hepatotoxicity in HIV-infected individuals (P=0.004, OR=2.67) owing to synergistic effect of these genes. Individuals with GSTT1-null and GSTM1-null genotypes showed higher risk of hepatotoxicity with advanced stage of (CD4<200) of HIV infection (P=0.18, OR=1.39; P=0.63, OR=1.13). In case-only analysis, GSTT1-null genotype among alcohol users showed elevated risk of hepatotoxicity in HIV-infected individuals (P=0.12, OR=1.36, 95% confidence interval (CI): 0.94–1.97) as compared with GSTT1 genotypes. The carriers GSTM1-null+GSTT1-null genotype among nevirapine user showed prominent risk of hepatotoxicity in HIV-infected individuals (P=0.12, OR=4.21, 95% CI: 0.60–29.54). Hence, we can conclude that GSTT1-null and GSTM1-null genotypes alone and in combination may predict the acquisition of hepatotoxicity.

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Acknowledgements

We thank all the clinic staff for sample collection. This study was supported by a research grant provided by ICMR, India.

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Authors and Affiliations

  1. Department of Molecular Biology, National AIDS Research Institute, Pune, India

    H O Singh, S Lata & V Nema

  2. Department of Clinical Sciences, National AIDS Research Institute, Pune, India

    M Angadi, S Bapat, J Pawar, M V Ghate, S Sahay & R R Gangakhedkar

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  1. H O Singh
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Correspondence to H O Singh.

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Singh, H., Lata, S., Angadi, M. et al. Impact of GSTM1, GSTT1 and GSTP1 gene polymorphism and risk of ARV-associated hepatotoxicity in HIV-infected individuals and its modulation. Pharmacogenomics J 17, 53–60 (2017). https://doi.org/10.1038/tpj.2015.88

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