TY - JOUR
T1 - Analysis of nucleotide diversity of NAT2 coding region reveals homogeneity across Native American populations and high intra-population diversity
AU - Fuselli, S.
AU - Gilman, R. H.
AU - Chanock, S. J.
AU - Bonatto, S. L.
AU - De Stefano, G.
AU - Evans, C. A.
AU - Labuda, D.
AU - Luiselli, D.
AU - Salzano, F. M.
AU - Soto, G.
AU - Vallejo, G.
AU - Sajantila, A.
AU - Pettener, D.
AU - Tarazona-Santos, E.
N1 - Funding Information:
We are grateful to the individuals who, contributing samples, made this study possible; to Cristina Fabbri, Guido Barbujani, Giorgio Bertorelle, Carolina Bonilla and two reviewers for criticisms, to Etienne Patin and Lluis Quintana-Murci for sharing data and to the Brazilian Fundac¸ão Nacional do Indio for logistic help. This study was partially funded by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil) to ET-S, FMS and SLB; the University of Bologna to DP, DL and ET-S; the Fundac¸ao de Amparo à Pesquisa do Estado de Rio Grande do Sul to FMS and SLB, and the Wellcome Trust to CAE.
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34147210676&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34147210676&partnerID=8YFLogxK
U2 - 10.1038/sj.tpj.6500407
DO - 10.1038/sj.tpj.6500407
M3 - Article
C2 - 16847467
AN - SCOPUS:34147210676
SN - 1470-269X
VL - 7
SP - 144
EP - 152
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
IS - 2
ER -