Please use this identifier to cite or link to this item: http://ds.saudeindigena.icict.fiocruz.br/handle/bvs/5999
Title: Factors associated with anti-TB drug-induced hepatotoxicity and genetic polymorphisms in indigenous and non-indigenous populations in Brazil
Authors: Heinrich, Melissa M.
Zembrzuski, Verônica M.
Ota, Marcos M.
Sacchi, Flavia P.
Teixeira, Raquel L. F.
Cabello Acero, Pedro H.
Cunha, Geraldo Marcelo
Souza-Santos, Reinaldo
Croda, Julio
Basta, Paulo C.
Abstract: Summary Anti-tuberculosis (TB) drugs are responsible for the occurrence of several adverse drug reactions (ADRs), including hepatotoxicity. The aim was to estimate the incidence of hepatotoxicity and its association with genetic polymorphisms and clinical-epidemiological factors by comparing indigenous and non-indigenous TB patients. We investigated clinical-epidemiological variables, serum levels of liver enzymes and NAT2, CYP2E1 and GSTM1 polymorphisms. A non-conditional logistic regression was used to identify the factors associated with hepatotoxicity. Odds ratios were used as the association measures. The incidence of hepatotoxicity was 19.7% for all patients. The risk of hepatotoxicity was almost four times higher in indigenous patients, comparing to non-indigenous. We identified a new nonsynonymous single nucleotide polymorphism of NAT2 in indigenous patients. In total, 54.6% of the patients expressed a slow acetylation phenotype profile. The frequency of the null genotype of GSTM1 was higher in non-indigenous patients (p = 0.002), whereas no significant differences in relation to polymorphisms of CYP2E1 were observed between the groups. Hepatotoxicity was associated with patients older than 60 and indigenous (OR = 26.0; 95%CI:3.1–217.6; OR = 3.8; 95%CI:1.3–11.1, respectively). Furthermore, hepatotoxicity was associated with a slow acetylation profile in indigenous patients (OR = 10.7; 95%CI:1.2–97.2). Our findings suggest that there are distinct acetylation profiles in the Brazilian population, emphasizing the importance of pharmacogenetic analyses for achieving personalized therapeutic schemes and better outcomes.
Keywords: Brazil
Health of Indigenous Peoples
Indians, South American
Tuberculosis
Pharmacogenetics
Adverse Drug Reactions
Hepatotoxicit
DeCS: Brasil
Saúde de Populações Indígenas
Índios Sul-Americanos
Epidemiologia
Tuberculose
Genética Humana
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
Issue Date: 2016
Publisher: Elsevier
Citation: HEINRICH, Melissa M.; ZEMBRZUSKI, Verônica M.; OTA, Marcos M.; SACCHI, Flavia P.; TEIXEIRA, Raquel L. F.; CABELLO ACERO, Pedro H.; CUNHA, Geraldo Marcelo; SOUZA-SANTOS, Reinaldo; CRODA, Julio; BASTA, Paulo C.. Factors associated with anti-TB drug-induced hepatotoxicity and genetic polymorphisms in indigenous and non-indigenous populations in Brazil. Tuberculosis, v. 101, p. 15-24, 2016
metadata.dc.identifier.doi: 10.1016/j.tube.2016.07.006
ISSN: 1472-9792
Copyright: open access
Appears in Collections:GH - Artigos de Periódicos

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