title: Analysis of six SNPs of NAT2 in Ngawbe and Embera Amerindians of Panama and determination of the Embera acetylation phenotype using caffeine.
abstract: 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.
authors.affiliation: DNA and Human Genomics Institute, University of Panama, Panama, Republic of Panama.
authors.forename: Lucia F
authors.initials: LF
authors.lastname: Jorge-Nebert
authors.forename: Michel
authors.initials: M
authors.lastname: Eichelbaum
authors.forename: Ernst-U
authors.initials: EU
authors.lastname: Griese
authors.forename: Ted
authors.initials: T
authors.lastname: Inaba
authors.forename: Tomas D
authors.initials: TD
authors.lastname: Arias
mesh_terms: D000107:Acetylation; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D002110:Caffeine; D019143:Evolution, Molecular; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007197:Indians, Central American / Q000235:genetics*; D007199:Indians, South American / Q000235:genetics*; D008957:Models, Genetic; D010176:Panama; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D002110:Caffeine; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human