Analysis of six SNPs of NAT2 in Ngawbe and Embera Amerindians of Panama and determination of the Embera acetylation phenotype using caffeine

Pharmacogenetics. 2002 Jan;12(1):39-48. doi: 10.1097/00008571-200201000-00006.


Six NAT2 single-nucleotide polymorphisms (SNPs) were analysed in 105 unrelated Ngawbe and 136 unrelated Embera Amerindians (482 chromosomes) by SNP-specific polymerase chain reaction analysis. 282C>T was the most common synonymous mutation, while 857G>A was the most frequent nonsynonymous inactivating exchange. The allelic frequency of the NAT2*5 series (containing the 341T>C exchange) was 2.4% and 9.9% for Ngawbe and Embera, respectively, five- to 20-times lower than that in Caucasians. The NAT2*6 series (590G>A) showed allelic frequencies of 0% and 3.7%, eight- to 30-times lower than in Caucasians. On the other hand, the NAT2*7 series, characterized by mutation 857G>A, had allelic frequencies (23.3% and 22.8%) that were 10-20-times higher in Amerindians than in Caucasians. Amerindians are characterized by decreased genetic diversity because they display a low number of mutated alleles (four and five for Ngawbe and Embera, respectively) that are present at low proportions (27.6% and 39%), reduced genotypic variability (seven out of 15 and 12 out of 21 possible genotypes) and low heterozygosity (40% and 55.1%) at the NAT2 locus. The NAT2 phenotype was evaluated with caffeine in a subset of 72 Embera. There were no disagreements between genotype and phenotype among rapid and slow acetylators (13/72, 18%). We conclude that, in the Embera, the analysis of three inactivating mutations was sufficient in predicting the phenotype in more than 99.5% of these subjects. NAT2 would appear to be of a selectively neutral character given that there is no evidence of adaptation to the prevailing ecology in Amerindians.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Arylamine N-Acetyltransferase / genetics*
  • Caffeine*
  • Evolution, Molecular
  • Gene Frequency
  • Genetic Variation
  • Genotype
  • Humans
  • Indians, Central American / genetics*
  • Indians, South American / genetics*
  • Models, Genetic
  • Panama
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics*
  • Selection, Genetic


  • Caffeine
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human