Genotyping of the polymorphic N-acetyltransferase (NAT2*) gene locus in two native African populations.
The hepatic N-acetyltransferase enzyme encoded by the NAT2* gene locus is responsible for the human polymorphic acetylation of numerous arylamine or hydrazine-containing drugs and xenobiotics including AIDS-related therapeutic agents such as isoniazid and sulphonamides. The genetic basis underlying the human acetylation polymorphism has been extensively studied in several populations but native African populations were poorly documented. In the present study, 117 unrelated black Africans, namely Dogons from Mali and Gabonese, were investigated for NAT2* allelic variability and genotype distribution. Thirteen NAT2* alleles were unambiguously identified by combined use of allele-specific reamplifications and restriction endonuclease digestions. Our results confirm the African origin of G191->A substitution in the NAT2* coding region which was previously associated with slow acetylation in African-Americans. The finding of high allelic diversity in the studied populations is consistent with the hypothesis of a single African origin for NAT2*-associated polymorphism. Finally, no excess of the slow acetylator phenotype is predicted in these populations, implying no need for fitting NAT2* polymorphism-sensitive therapies to black Africans, compared to Caucasians.
Deloménie
C
C
INSERM U120, Hospital Robert Debre, Paris, France.
Sica
L
L
Grant
D M
DM
Krishnamoorthy
R
R
Dupret
J M
JM
D000107:Acetylation; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005681:Gabon; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008099:Liver / Q000201:enzymology; D008302:Mali; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics; D001741:Black or African American
D017931:DNA Primers; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human