N-acetyltransferase 2 enzyme genotype–phenotype discordances in both HIV-negative and HIV-positive Nigerians

Abstract

Background: The N-acetyltransferase 2 (NAT2) enzyme has been understudied in Nigerians including genotype-phenotype association studies. Objective: Study objective was NAT2 haplotype identification and genotype-phenotype investigations in HIV-positive and HIV-negative Nigerians. Method: Phenotypes included self-reported sulphonamide hypersensitivity survey, experimental and computational NAT2 phenotyping. NAT2 gene was amplified via polymerase chain reaction. Gene sequencing employed ABI 3730 and Haploview 4.2 for haplotype reconstruction. Genotypephenotype analyses used Chi square p-value and odds ratio with 95% confidence interval. Results: Self-reported sulphonamide hypersensitivity revealed 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 857 G>A were not significantly different between both groups (OR 0.87 95%CI 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 > 1% while NAT2*12B had 1.1% in HIV-positive and 0.4% in HIV-negative group. Overall, slow acetylator haplotypes made up 68%. NAT2*12 signature SNP (sSNP) was in high linkage

Genotype-Environment Interaction Analysis of NQO1, CYP2E1, and NAT2 Polymorphisms and the Risk of Childhood Acute Lymphoblastic Leukemia: A Report From the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

“…Due the differences in the NAT2 SNPs and haplotype frequencies among the populations, this new method is no applicable in very heterogenous ethnic groups, such as Mexican. In addition, it has been reported a genotype-phenotype discordance (47,48). It is well-known that the acetylation phenotype is affected either by NAT2 genetic variants or by environmental variables.…”

Non‐compartmental and population pharmacokinetic analysis of dapsone in healthy NIGERIANS: A pilot study

“…Pregnant females and individuals on any antimalarial therapy were excluded from the study. The data for this study were collected as part of a larger study which focused on NAT2 genotype–phenotype correlation in Nigerians 15 . The study was approved by the University of Ibadan/University College Hospital Ethics Committee with protocol number UI/EC/10/0021.…”

“…The data for this study were collected as part of a larger study which focused on NAT2 genotypephenotype correlation in Nigerians. 15 The study was approved by the Plasma concentrations of dapsone and its metabolite, monoacetyldapsone (MADDS) were determined using high-performance liquid chromatography (HPLC) adapted from the method of Alfirevic et al 16 The lower limit of quantification (LLOQ) was 0.201 μg/mL. NAT2 phenotype was determined as the metabolic ratio of MADDS to dapsone ≥ 3 h post-drug administration.…”

Pharmacogenomics of Allopurinol and Sulfamethoxazole/Trimethoprim: Case Series and Review of the Literature

“…In contrast, the NAT2 slow acetylator phenotype occurs in only 9% of Serbians [ 10 ]. Considering people of African descent, compared to 44% of US Blacks with a NAT2 slow acetylator genotype [ 9 ], 68% of Nigerians are NAT2 slow acetylators [ 11 ]. Similarly, in Asian populations, the frequency of NAT2 slow acetylator phenotype is higher in Thai populations (50%) compared to a frequency of 5–20% in other Asian populations (Japan, Korea, China) [ 12 ].…”