The distribution of allelic and genotypic frequencies of N-Acetyltransferase-2 variants in an Argentine population

Julián Gabriel Chamorro,Federico Manuel Aranda,Gabriela Fernanda De Larrañaga,Jorge P Castagnino,Rosa M Musella,Ana Frias

doi:10.3855/jidc.2111

Julián Gabriel Chamorro, Federico Manuel Aranda + Show 4 more

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https://doi.org/10.3855/jidc.2111

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Abstract

Arylamine N-acetyltransferase-2 (NAT-2) is a key human enzyme in drug detoxification and elimination. Mutations in NAT-2 affect the activity of anti-tuberculosis drugs and result in three different phenotypes: rapid (RA), intermediate (IA) and slow acetylators (SA). The allelic, genotypic and phenotypic frequencies of NAT-2 were studied in 185 patients from Buenos Aires by restriction fragment length polymorphism. The following allele frequencies were obtained: *4 = 29.9%, *5 = 37.0, *6 = 25.6%, *7 = 8% and *14 = 1.3%. With regard to the phenotype, we observed that 53.6% of the population was SA, 35.7% was IA and 10.7% was RA. A high prevalence of SA might have an impact on anti-TB drug-induced hepatotoxicity.

Highlights

Arylamine N-acetyltransferase-2 (NAT-2) is a key human enzyme in drug detoxification and elimination
Arylamine N-acetyltransferase-2 (NAT-2) is a cytosolic phase II conjugation enzyme that plays a key role in the detoxification and elimination of many commonly prescribed drugs through acetylation, and it is involved in the metabolism of carcinogens from environmental, industrial and dietary sources [1]
INH, a substrate of NAT-2, is a first-line drug used in tuberculosis (TB) treatment, and it is considered to be responsible for adverse drug reactions that lead to hepatotoxicity [6,8,9]

Summary

Introduction

Arylamine N-acetyltransferase-2 (NAT-2) is a key human enzyme in drug detoxification and elimination. Some of these mutations affect the activity of the enzyme resulting in three different phenotypes: rapid acetylators (RA), intermediate acetylators (IA) and slow acetylators (SA) [3]. An association between NAT-2 acetylation polymorphism and INH-induced hepatotoxicity has been reported by several studies, considerable controversies remain as a consequence of the wide variability in the results of these studies [5,6,8,9].

Results

Conclusion