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

S. Fuselli, Robert H Gilman, S. J. Chanock, S. L. Bonatto, G. De Stefano, C. A. Evans, D. Labuda, D. Luiselli, F. M. Salzano, G. Soto, G. Vallejo, A. Sajantila, D. Pettener, E. Tarazona-Santos

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)144-152
Number of pages9
JournalPharmacogenomics Journal
Volume7
Issue number2
DOIs
StatePublished - Apr 2007

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Acetyltransferases
North American Indians
Nucleotides
Population
Siberia
Sulfamethoxazole
Chromosomes, Human, Pair 13
Latin America
Clinical Pharmacology
Isoniazid
Population Genetics
Haplotypes
Amines
Pharmacokinetics
Anti-Bacterial Agents
Diet
Phenotype
Enzymes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics

Cite this

Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity. / Fuselli, S.; Gilman, Robert H; Chanock, S. J.; Bonatto, S. L.; De Stefano, G.; Evans, C. A.; Labuda, D.; Luiselli, D.; Salzano, F. M.; Soto, G.; Vallejo, G.; Sajantila, A.; Pettener, D.; Tarazona-Santos, E.

In: Pharmacogenomics Journal, Vol. 7, No. 2, 04.2007, p. 144-152.

Research output: Contribution to journalArticle

Fuselli, S, Gilman, RH, Chanock, SJ, Bonatto, SL, De Stefano, G, Evans, CA, Labuda, D, Luiselli, D, Salzano, FM, Soto, G, Vallejo, G, Sajantila, A, Pettener, D & Tarazona-Santos, E 2007, 'Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity', Pharmacogenomics Journal, vol. 7, no. 2, pp. 144-152. https://doi.org/10.1038/sj.tpj.6500407
Fuselli, S. ; Gilman, Robert H ; Chanock, S. J. ; Bonatto, S. L. ; De Stefano, G. ; Evans, C. A. ; Labuda, D. ; Luiselli, D. ; Salzano, F. M. ; Soto, G. ; Vallejo, G. ; Sajantila, A. ; Pettener, D. ; Tarazona-Santos, E. / Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity. In: Pharmacogenomics Journal. 2007 ; Vol. 7, No. 2. pp. 144-152.
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