Determination of NAT2 acetylation status in the Greenlandic population

Arch Toxicol. 2016 Apr;90(4):883-9. doi: 10.1007/s00204-015-1501-1. Epub 2015 Mar 21.

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.

Keywords: Greenland; Inuit ancestry; Isoniazid; N-acetyltransferase 2; Tuberculosis treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adolescent
  • Adult
  • Aged
  • Antitubercular Agents / pharmacokinetics
  • Arylamine N-Acetyltransferase / genetics*
  • Arylamine N-Acetyltransferase / metabolism*
  • Female
  • Genetics, Population
  • Greenland
  • Humans
  • Inactivation, Metabolic / genetics
  • Isoniazid / pharmacokinetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • White People / genetics
  • Young Adult

Substances

  • Antitubercular Agents
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human
  • Isoniazid