Study of NAT2 genetic polymorphism in West African subjects: example of an healthy non-smoker Senegalese population.

ABSTRACT

The NAT2 genetic polymorphism determines the individual acetylator status and, consequently, the capacity to metabolize, or not, drugs and xenobiotics which are substrates of NAT2. As the nature and frequency of the NAT2 polymorphisms vary remarkably between populations of different ethnic origins, genotyping strategies used to predict the acetylation phenotype need to be adapted for each particular population regarding their genetic backgrounds at this locus. As few data on the genetic polymorphism of NAT2 are available in the Senegalese population, we performed an extensive identification of NAT2 variants in 105 healthy non-smoker Senegalese subjects by direct PCR sequencing of the coding region. Eleven previously described SNPs were identified in this Senegalese population. Upon allele analysis, the four most frequent alleles were of the NAT2*5- (35.7 %), NAT2*6- (21.0 %), NAT2*12- (16.7 %) and NAT2*14- (10.0 %) type, the remaining alleles, including the wild-type NAT2*4, having each a frequency lower than 10 %. According to the observed genotypes, 51 and 50 subjects were predicted to be of the rapid (48.6 %) and slow (47.6 %) acetylator phenotype, respectively, while four individuals (3.8 %) were considered of unknown phenotype as they carry at least one allele with a yet unknown functional effect. These baseline data would be of particular interest to set up an efficient genotyping strategy to predict the acetylation status of Senegalese patients with tuberculosis and, thus, to optimize their isoniazid treatment.