Genetic Polymorphisms of N-acetyl Transferase 2 and the Risk of Hepatotoxicity in Patients on Isoniazid Preventive Therapy at Kenyatta National Hospital

Abstract

Abstract Background N-acetyl transferase (NAT2) affects metabolism and disposition of isoniazid. Polymorphisms of NAT2 may affect pharmacokinetics of isoniazid (INH) by decreasing concentration of active drug in fast acetylators. High concentrations of drug in slow acetylators may lead to hepatotoxicity; this affects clinical outcomes of patients on therapy. Objectives The main objective was to characterize the distribution of selected single nucleotide polymorphisms (SNPs) of NAT2 in patients on IPT at the Comprehensive Care Centre (CCC) of Kenyatta National Hospital (KNH) and to investigate for a relationship between acetylator status and isoniazid induced hepatotoxicity (as indicated by elevated ALT levels). Methods The study design was a cross sectional study and entailed collection of patient data. The QIAamp ® DNA Mini kit was used for extraction of DNA and purification of Genomic DNA, followed by DNA sequencing. Data analysis was conducted using SPSS version 25(IBM USA). Results The prevalence of the homozygous NAT2 genotype was 19% and that of the heterozygous genotype was 50%. The proportion of the population with slow acetylator alleles was 56% and the proportion of fast acetylator alleles was 44%. Fisher's exact test showed no significant association between ALT levels and NAT2 genotype (P = 0.330). Conclusion The study found no significant association between NAT2 genotypes and ALT levels (P = 0.33)