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Individual susceptibility to arsenic-induced diseases: the role of host genetics, nutritional status, and the gut microbiome

Mammalian Genome volume 29, pages 63–79 (2018)Cite this article

Abstract

Arsenic (As) contamination in water or food is a global issue affecting hundreds of millions of people. Although As is classified as a group 1 carcinogen and is associated with multiple diseases, the individual susceptibility to As-related diseases is highly variable, such that a proportion of people exposed to As have higher risks of developing related disorders. Many factors have been found to be associated with As susceptibility. One of the main sources of the variability found in As susceptibility is the variation in the host genome, namely, polymorphisms of many genes involved in As transportation, biotransformation, oxidative stress response, and DNA repair affect the susceptibility of an individual to As toxicity and then influence the disease outcomes. In addition, lifestyles and many nutritional factors, such as folate, vitamin C, and fruit, have been found to be associated with individual susceptibility to As-related diseases. Recently, the interactions between As exposure and the gut microbiome have been of particular concern. As exposure has been shown to perturb gut microbiome composition, and the gut microbiota has been shown to also influence As metabolism, which raises the question of whether the highly diverse gut microbiota contributes to As susceptibility. Here, we review the literature and summarize the factors, such as host genetics and nutritional status, that influence As susceptibility, and we also present potential mechanisms of how the gut microbiome may influence As metabolism and its toxic effects on the host to induce variations in As susceptibility. Challenges and future directions are also discussed to emphasize the importance of characterizing the specific role of these factors in interindividual susceptibility to As-related diseases.

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Acknowledgements

We are grateful to all investigators for their important contributions in the field. This review is by no means a complete list of all relevant studies due to the length and scope of the paper. The work is supported by the National Institute of Health/National Institute of Environmental Health Sciences (R01ES024950).

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Authors and Affiliations

  1. Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Liang Chi, Pengcheng Tu, Chih-Wei Liu, Jingchuan Xue, Yunjia Lai & Kun Lu

  2. NIH West Coast Metabolomics Center, University of California, Davis, CA, 95616, USA

    Bei Gao

  3. Department of Population Health and Pathobiology, North Carolina State University, Raleigh, NC, 27607, USA

    Hongyu Ru

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  1. Liang Chi
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  2. Bei Gao
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  3. Pengcheng Tu
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Correspondence to Kun Lu.

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Chi, L., Gao, B., Tu, P. et al. Individual susceptibility to arsenic-induced diseases: the role of host genetics, nutritional status, and the gut microbiome. Mamm Genome 29, 63–79 (2018). https://doi.org/10.1007/s00335-018-9736-9

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  • DOI: https://doi.org/10.1007/s00335-018-9736-9

Keywords

  • Host Genetics
  • Interindividual Susceptibility
  • iAsIII
  • Arsenic (+ 3) Methyltransferase (AS3MT)
  • Methylenetetrahydrofolate Reductase (MTHFR)