BackgroundThe N-acetyltransferase 2 (NAT2) enzyme has been understudied in Nigerians including genotype-phenotype association studies.ObjectiveThe aim of this study was NAT2 haplotype identification and genotype-phenotype investigations in HIV-positive and HIV-negative Nigerians.Patients and methodsPhenotypes included self-reported sulphonamide hypersensitivity survey, experimental and computational NAT2 phenotyping. The NAT2 gene was amplified by PCR. Gene sequencing used ABI 3730 and Haploview 4.2 for haplotype reconstruction. Genotype-phenotype analyses used the χ2 P-value and odds ratio with a 95% confidence interval.ResultsSelf-reported sulphonamide hypersensitivity showed a prevalence of 3.1 and 12.4% in HIV-positive and HIV-negative Nigerians, respectively. NAT2 genetic variants 191G>A, 282C>T, 341T>C, 481C>T, 590G>A, 803A>G and 857G>A were not significantly different between both groups (odds ratio=0.87; 95% confidence interval: 0.54-1.38, P=0.55). Nine haplotypes: NAT2∗4, NAT2∗12A, NAT2∗13A, NAT2∗5B, NAT2∗6A, NAT2∗7B, NAT2∗5C, NAT2∗14B and NAT2∗14A had frequencies more than 1%, whereas NAT2∗12B had 1.1% in the HIV-positive and 0.4% in the HIV-negative group. Overall, slow acetylator haplotypes made up 68%. The NAT2∗12 signature single-nucleotide polymorphism was in high linkage disequilibrium with signature single-nucleotide polymorphism for NAT2∗13 (D′=0.97, r2=0.61) and NAT2∗5 (D′=0.98, r2=0.64). Genotype-phenotype association analysis showed haplotypes NAT2∗13A, NAT2∗5C, NAT2∗7B and NAT2∗14A to be associated strongly with the slow metabolic phenotype (P=0.002, 0.029, 0.032 and 0.050, respectively). Computational phenotypes were similar, with 30.9, 66 and 3.1% for slow, intermediate and rapid acetylators, respectively, among HIV-positive Nigerians and 31.2, 66.3 and 2.5% among the HIV-negative group. Overall, slow phenotypes made up 31%.ConclusionNAT2 haplotype frequencies are similar in Nigerians, irrespective of HIV status, but genotype-phenotype discordances exist.
