title: Determination of NAT2 acetylation status in the Greenlandic population.
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.
authors: Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen S, Denmark. fge@ssi.dk.
authors: Frank
authors: F
authors: Geller
authors: Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen S, Denmark.
authors: Bolette
authors: B
authors: Soborg
authors: Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen S, Denmark.
authors: Anders
authors: A
authors: Koch
authors: Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen S, Denmark.
authors: Sascha Wilk
authors: SW
authors: Michelsen
authors: Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen S, Denmark.
authors: Karen
authors: K
authors: Bjorn-Mortensen
authors: Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen S, Denmark.
authors: Lisbeth
authors: L
authors: Carstensen
authors: Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen S, Denmark.
authors: Emilie
authors: E
authors: Birch
authors: Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen S, Denmark.
authors: Anne Christine
authors: AC
authors: Nordholm
authors: Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen S, Denmark.
authors: Marie Mila Broby
authors: MM
authors: Johansen
authors: Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen S, Denmark.
authors: Malene Landbo
authors: ML
authors: Børresen
authors: Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen S, Denmark.
authors: Bjarke
authors: B
authors: Feenstra
authors: Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen S, Denmark.|Department of Clinical Medicine, University of Copenhagen, 2200, Copenhagen N, Denmark.|Department of Medicine, Stanford School of Medicine, Stanford, CA, 94305, USA.
authors: Mads
authors: M
authors: Melbye
mesh_terms: D000107:Acetylation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000493:pharmacokinetics; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005828:Genetics, Population; D006116:Greenland; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D007538:Isoniazid / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid
keywords: Greenland; Inuit ancestry; Isoniazid; N-acetyltransferase 2; Tuberculosis treatment