Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs

BACKGROUND Distinct N-acetyltransferase 2 (NAT2) slow acetylators genotypes have been associated with a higher risk to develop anti-tuberculosis drug-induced hepatotoxicity (DIH). However, studies have not pointed the relevance of different acetylation phenotypes presented by homozygotes and compound heterozygotes slow acetylators on a clinical basis. OBJECTIVES This study aimed to investigate the association between NAT2 genotypes and the risk of developing DIH in Brazilian patients undergoing tuberculosis treatment, focusing on the discrimination of homozygotes and compound heterozygotes slow acetylators. METHODS/FINDINGS The frequency of NAT2 genotypes was analysed by DNA sequencing in 162 patients undergoing tuberculosis therapy. The mutation analyses revealed 15 variants, plus two new NAT2 mutations, that computational simulations predicted to cause structural perturbations in the protein. The multivariate statistical analysis revealed that carriers of NAT2*5/*5 slow acetylator genotype presented a higher risk of developing anti-tuberculosis DIH, on a clinical basis, when compared to the compound heterozygotes presenting NAT2*5 and any other slow acetylator haplotype [aOR 4.97, 95% confidence interval (CI) 1.47-16.82, p = 0.01]. CONCLUSION These findings suggest that patients with TB diagnosis who present the NAT2*5B/*5B genotype should be properly identified and more carefully monitored until treatment outcome in order to prevent the occurrence of anti-tuberculosis DIH.

Relationship between polymorphism of arylamine N-acetyltransferase 2 and genetic susceptibility to hair dye dermatitis / 中华医学美学美容杂志

Objective To investigate the relationship between polymorphism of arylamine N-acetyltransferase 2 (NAT2) and hair dye dermatitis in a Chinese population. Methods Polymorphism chain-restriction fragment length polymorphism (PCR-RFLP) was used and the wild-type allele (NAT2 * 4) and three mutant alleles (NAT2 * 5A, 6B and 7A) were determined in 60 patients with hair dye dermatitis and 73 age-matched control subjects in Tianjin region. Results In hair dye dermatitis cases, the frequency of NAT2 * 4, NAT2 * 5A, NAT2 * 6B, NAT2 * 7A was 52. 5 % , 5. 0 % ,26.7 % and 15. 8 %, respectively, and no statistically significant difference of the frequencies was found between the hair dye dermatitis patients and controls (P>0. 05). The frequency of rapid genotype, intermediate genotype and slow genotype was 26. 7 % , 51. 7 % and 21. 7 % in hair dye dermatitis cases, 30. 1 %, 50. 7 % and 19. 2 % in control subjects, respectively, and no statistically significant difference of the frequencies between the two groups (P>0. 05). Conclusions Our study suggests that there might be no relationship between polymorphism of NAT2 and genetic susceptibility to hair dye dermatitis in a Chinese population.