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Determination of NAT2 acetylation status in the Greenlandic population

  • Toxicogenomics
  • Published:
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Abstract

N-acetyltransferase 2 (NAT2) is a well-studied phase II xenobiotic metabolizing enzyme relevant in drug metabolism and cancerogenesis. NAT2 activity is largely determined by genetic polymorphisms in the coding region of the corresponding gene. We investigated NAT2 acetylation status in 1556 individuals from Greenland based on four different single nucleotide polymorphism (SNP) panels and the tagging SNP rs1495741. There was good concordance between the NAT2 status inferred by the different SNP combinations. Overall, the fraction of slow acetylators was low with 17.5 % and varied depending on the degree of Inuit ancestry; in individuals with <50 % Inuit ancestry, we observed more than 25 % slow acetylators reflecting European ancestry. Greenland has a high incidence of tuberculosis, and individual dosing of isoniazid according to NAT2 status has been shown to improve treatment and reduce side effects. Our findings could be a first step in pharmacogenetics-based tuberculosis therapy in Greenland.

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Acknowledgments

We thank all study participants for their cooperation in this study, as well as all individuals involved in collecting and handling of data and samples. We thank Mikael Andersson (data management), Poul Berger, Henrik Hjalgrim, Mikkel Koch, Jacqueline M. Mistry, Helle Møller and Johan E. Navne (all field-work). Sascha Wilk Michelsen and Karen Bjorn-Mortensen are both supported by Commission for Scientific Research in Greenland/Danish Research Council scholarships, and Bjarke Feenstra is supported by an Oak Foundation fellowship. The study was conducted with support from: The Danish Research Council, The Greenlandic Ministry of Education, Church, Culture and Gender Equality, the Maersk foundation (Fonden til lægevidenskabens Fremme), and the Aase and Ejnar Danielsens Foundation.

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Authors and Affiliations

  1. Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen S, Denmark

    Frank Geller, Bolette Soborg, Anders Koch, Sascha Wilk Michelsen, Karen Bjorn-Mortensen, Lisbeth Carstensen, Emilie Birch, Anne Christine Nordholm, Marie Mila Broby Johansen, Malene Landbo Børresen, Bjarke Feenstra & Mads Melbye

  2. Department of Clinical Medicine, University of Copenhagen, 2200, Copenhagen N, Denmark

    Mads Melbye

  3. Department of Medicine, Stanford School of Medicine, Stanford, CA, 94305, USA

    Mads Melbye

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  1. Frank Geller
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  2. Bolette Soborg
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  3. Anders Koch
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Correspondence to Frank Geller.

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Geller, F., Soborg, B., Koch, A. et al. Determination of NAT2 acetylation status in the Greenlandic population. Arch Toxicol 90, 883–889 (2016). https://doi.org/10.1007/s00204-015-1501-1

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