Full-Gene-Sequencing Analysis of N-Acetyltransferase-2 in an Adult Indian Population

Aims: Drug-metabolizing enzymes play a major role in determining the outcome of drug therapy. N-acetyltransferase-2 (NAT2) is one of the main enzymes involved in metabolism of isoniazid used in treatment of tuberculosis (TB). Several variations in the NAT2 gene give rise to multiple haplotypes that phenotypically code for different acetylator status. The objective was to generate a more unambiguous picture of the NAT2 scenario in India as compared to that obtained from polymerase chain reaction-restriction fragment length polymorphism methods. Methods: Full-gene-sequencing analysis of NAT2 was carried out in 181 healthy Indian subjects from different regional groups. Results: A total of 33 diplotypes were recorded from six known single-nucleotide polymorphisms. The overall frequency of the slow acetylator haplotypes detected in this study was 65%, followed by 26% and 9% intermediate and rapid acetylators, respectively. Of the slow acetylator alleles, the NAT2*5B/*6A occurred in 25% of the study subjects. Conclusions: The study indicates that the frequency of slow acetylator alleles is high in the adult Indian population. Since the prevalence of TB is high in this population, pharmacogenetic testing for NAT2 alleles may be advisable before start of therapy with isoniazid to prevent drug toxicity.