title: Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity.
abstract: N-acetyltransferase 2 (NAT2), an important enzyme in clinical pharmacology, metabolizes antibiotics such as isoniazid and sulfamethoxazole, and catalyzes the transformation of aromatic and heterocyclic amines from the environment and diet into carcinogenic intermediates. Polymorphisms in NAT2 account for variability in the acetylator phenotype and the pharmacokinetics of metabolized drugs. Native Americans, settled in rural areas and large cities of Latin America, are under-represented in pharmacogenetics studies; therefore, we sequenced the coding region of NAT2 in 456 chromosomes from 13 populations from the Americas, and two from Siberia, detecting nine substitutions and 11 haplotypes. Variants *4 (37%), *5B (23%) and *7B (24%) showed high frequencies. Average frequencies of fast, intermediate and slow acetylators across Native Americans were 18, 56 and 25%, respectively. NAT2 intra-population genetic diversity for Native Americans is higher than East Asians and similar to the rest of the world, and NAT2 variants are homogeneously distributed across native populations of the continent.
authors.affiliation: Department of Forensic Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Fuselli
authors.forename: R H
authors.initials: RH
authors.lastname: Gilman
authors.forename: S J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: S L
authors.initials: SL
authors.lastname: Bonatto
authors.forename: G
authors.initials: G
authors.lastname: De Stefano
authors.forename: C A
authors.initials: CA
authors.lastname: Evans
authors.forename: D
authors.initials: D
authors.lastname: Labuda
authors.forename: D
authors.initials: D
authors.lastname: Luiselli
authors.forename: F M
authors.initials: FM
authors.lastname: Salzano
authors.forename: G
authors.initials: G
authors.lastname: Soto
authors.forename: G
authors.initials: G
authors.lastname: Vallejo
authors.forename: A
authors.initials: A
authors.lastname: Sajantila
authors.forename: D
authors.initials: D
authors.lastname: Pettener
authors.forename: E
authors.initials: E
authors.lastname: Tarazona-Santos
mesh_terms: D000107:Acetylation; D000569:Americas / Q000453:epidemiology; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D019143:Evolution, Molecular; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D009154:Mutation; D016366:Open Reading Frames; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012800:Siberia / Q000453:epidemiology
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human