Article
The role of cigarette smoking and liver enzymes polymorphisms in anti-tuberculosis drug-induced hepatotoxicity in brazilian patients
Registro en:
VALLE, Camila Zaverucha do et al. The role of cigarette smoking and liver enzymes polymorphisms in anti-tuberculosis drug-induced hepatotoxicity in brazilian patients. Tuberculosis, v.94, n.3, p.299–305, 2014.
1472-9792
10.1016/j.tube.2014.03.006
1873-281X
Autor
Valle, Camila Zaverucha do
Monteiro, Sérgio Pereira
El-Jaick, Kênia Balbi
Rosadas, Leonardo Azevedo da Silva
Costa, Marli Jane Martins
Quintana, Marcel de Souza Borges
Castro, Liane de
Resumen
Programa Estratégico de Apoio à Pesquisa em Saúde, Fundação Oswaldo Cruz, FAPERJ Tuberculosis (TB) is still a major health concern and side-effects related to the treatment, especially druginduced
hepatotoxicity (DIH), should be better investigated. In the present study, a possible association
between anti-TB DIH and cigarette smoking, N-acetyltransferase 2 (NAT2), Cytochrome P450 2E1 (CYP2E1)
and Cytochrome P450 3A4 (CYP3A4) genotypes was studied in 131 TB Brazilian patients. The NAT2 and
CYP3A4 genetic polymorphisms were determined using a polymerase chain reaction (PCR) direct
sequencing approach and genetic polymorphisms of CYP2E1 gene were determined by restriction fragment
length polymorphism (RFLP). The risk of anti-TB DIH was lower in rapid/intermediate acetylators when
compared to slowacetylators (OR: 0.34, CI 95: 0.16e0.71; p < 0.01). A decreased risk of developing anti-TB
DIH was also observed in active smokers when compared to non-smokers (OR: 0.28, 95 CI: 0.11e0.64;
p < 0.01). Significant association between CYP3A4 genotypes and hepatotoxicity was not observed, as well
as between CYP2E1 genotype and hepatotoxicity, whose frequency of patients with wild homozygous was
more prevalent. The anti-TB drugs interactions with smoking on hepatotoxicity, as well as the NAT2
phenotype, may require to adjust therapeutic regimen dosages or alarm in case of adverse event
developments.