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.

Fuselli, S., Gilman, R., Chanock, S., Bonatto, S., DE STEFANO, G., Evans, C., et al. (2007). Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity. PHARMACOGENOMICS JOURNAL, 7(2), 144-152 [10.1038/sj.tpj.6500407].

Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity

DE STEFANO, GIANFRANCO;
2007-01-01

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.
2007
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14 - FARMACOLOGIA
English
Con Impact Factor ISI
arylamine acetyltransferase; American Indian; article; gene locus; gene sequence; genetic isolation by distance; genetic variability; geographical variation (species); haplotype; human; nucleotide sequence; pharmacogenetics; phenotype; population genetics; priority journal; promoter region; russian federation; sequence analysis;western hemisphere; acetylation; americas; arylamine N-acetyltransferase; DNA mutational analysis; evolution, molecular; gene frequency; genetics, population; genotype; haplotypes; humans; Indians, North American; mutation; open reading frames; phenotype; polymorphism, single nucleotide
Fuselli, S., Gilman, R., Chanock, S., Bonatto, S., DE STEFANO, G., Evans, C., et al. (2007). Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity. PHARMACOGENOMICS JOURNAL, 7(2), 144-152 [10.1038/sj.tpj.6500407].
Fuselli, S; Gilman, R; Chanock, S; Bonatto, S; DE STEFANO, G; Evans, C; Labuda, D; Luiselli, D; Salzano, F; Soto, G; Vallejo, G; Sajantila, A; Pettene...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/8131
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