Sub-Saharan African coding sequence variation and haplotype diversity at the NAT2 gene

Hum Mutat. 2006 Jul;27(7):720. doi: 10.1002/humu.9438.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa South of the Sahara / epidemiology
  • Arylamine N-Acetyltransferase / genetics*
  • DNA Mutational Analysis
  • Geography
  • Haplotypes*
  • Humans
  • Mutation, Missense*
  • Phenotype
  • Point Mutation
  • Polymorphism, Single Nucleotide


  • Arylamine N-Acetyltransferase
  • NAT2 protein, human