Journal
HUMAN MUTATION
Volume 27, Issue 7, Pages 720-U114Publisher
WILEY-BLACKWELL
DOI: 10.1002/humu.9438
Keywords
NAT2; arylamine N-acetyltransferase 2; single-nucleotide polymorphisms; populations; Pygmies; Bantus; Africa; acetylation; isoniazid; association study
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Funding
- Agence Nationale de la Recherche (ANR) [ANR-05-JCJC-0124-01, 2004 - PRO-0050]
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A total of 530 chromosomes from 12 sub-Saharan African populations were sequenced at the human arylamine N-acetyltransferase NAT2 gene. We identified seven novel non-synonymous mutations observed at low frequencies (<11%) in our African multi-ethnic panel. By using algorithms based on evolutionary conservation, two mutations (c.70T>A [p.L24I] and c.578C>T [p.T193M]) for which the activity of their encoded protein has never been determined, were predicted to entail a potentially damaging effect on protein activity. In addition, approximately 5% of the overall NAT2 African haplotypes presented an unknown functional effect. More interestingly, NAT2 haplotype frequencies and acetylation status inference revealed that the hunter-gatherer Western Pygmies and ! Kung San were mainly composed of fast and intermediate acetylators, in clear contrast with most agriculturalist populations. These observations highlight the need of a detailed genetic characterization of African populations at this locus to adapt medical treatment, such as the antitubercular isoniazid, to individual/population make-up in the most effective manner. (C) 2006 Wiley-Liss, Inc.
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