CYP3A4*1B and NAT2*14 alleles in a native African population.
Single nucleotide polymorphisms were examined in the cytochrome 450 3A4 (CYP3A4) and N-acetyltransferase 2 (NAT2) genes, which code for major mediators of the metabolism of a wide variety of therapeutic drugs, as well as xenobiotics. We determined, in a population from Guinea-Bissau, the frequencies of CYP3A4 and NAT2 variants expected to be prevalent among Africans, due to the high frequency previously observed in African Americans. The observed frequencies were 72% for CYP3A4*1B and 19.2% for the NAT2 191 G>A variant. The high frequency found for these potentially function-altering polymorphisms suggests the possibility of impaired metabolism through CYP3A4 and NAT2 in this population. Strikingly, the frequency observed for the NAT2 191 G>A single nucleotide polymorphism (SNP), associated with the slow acetylator phenotype, was significantly higher than found in other African populations, suggesting the existence of a west to east gradient across Sub-Saharan Africa. The prevalence of these variants may be relevant with regard to therapeutic efficacy in African populations for it may potentially affect drug clearance and consequently, increase the incidence of side effects and drug-drug interactions.
Cavaco
Isa
I
Laboratory of Molecular Toxicology, CMQA, Faculdade de Ciências e Tecnologia, University of Algarve, Faro, Portugal.
Reis
Rita
R
Gil
J Pedro
JP
Ribeiro
Vera
V
D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D001741:Black or African American
D017931:DNA Primers; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human