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Mitochondrial DNA Haplogroup A Decreases the Risk of Drug Addiction but Conversely Increases the Risk of HIV-1 Infection in Chinese Addicts

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Abstract

Drug addiction is one of the most serious social problems in the world today and addicts are always at a high risk of acquiring HIV infection. Mitochondrial impairment has been reported in both drug addicts and in HIV patients undergoing treatment. In this study, we aimed to investigate whether mitochondrial DNA (mtDNA) haplogroup could affect the risk of drug addiction and HIV-1 infection in Chinese. We analyzed mtDNA sequence variations of 577 Chinese intravenous drug addicts (289 with HIV-1 infection and 288 without) and compared with 2 control populations (n = 362 and n = 850). We quantified the viral load in HIV-1-infected patients with and without haplogroup A status and investigated the potential effect of haplogroup A defining variants m.4824A > G and m.8794C > T on the cellular reactive oxygen species (ROS) levels by using an allotopic expression assay. mtDNA haplogroup A had a protective effect against drug addiction but appeared to confer an increased risk of HIV infection in addicts. HIV-1-infected addicts with haplogroup A had a trend for a higher viral load, although the mean viral load was similar between carriers of haplogroup A and those with other haplogroup. Hela cells overexpressing allele m.8794 T showed significantly decreased ROS levels as compared to cells with the allele m.8794C (P = 0.03). Our results suggested that mtDNA haplogroup A might protect against drug addiction but increase the risk of HIV-1 infection. The contradictory role of haplogroup A might be caused by an alteration in mitochondrial function due to a particular mtDNA ancestral variant.

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Acknowledgments

We thank all participants in this study. We thank Dr. Califano and Dr. Corral-Debrinski for sharing the plasmids and Miss Dandan Yu for the technical help. This study was supported by the National Natural Science Foundation of China (grant number 31171225), the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (grant number XDB02020003), and the Ministry of Science and Technology of China (grant number 2011CB910900).

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    Authors and Affiliations

    1. Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, China

      A-Mei Zhang, Qiu-Xiang Hu, Feng-Liang Liu, Rui Bi, Wen Zhang, Hao Guo, Yong-Tang Zheng & Yong-Gang Yao

    2. Department of Laboratory Medicine Science, Dehong Prefecture People’s Hospital of Yunnan Province, Yunnan, China

      Bi-Qing Yang

    3. Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China

      Hao Guo

    4. Exmouth, Devon, UK

      Ian Logan

    5. Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China

      Yong-Tang Zheng & Yong-Gang Yao

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    A-Mei Zhang and Qiu-Xiang Hu contributed equally to this work.

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    Zhang, AM., Hu, QX., Liu, FL. et al. Mitochondrial DNA Haplogroup A Decreases the Risk of Drug Addiction but Conversely Increases the Risk of HIV-1 Infection in Chinese Addicts. Mol Neurobiol 53, 3873–3881 (2016). https://doi.org/10.1007/s12035-015-9323-y

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