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Relationship of anti-tuberculosis drug-induced liver injury and genetic polymorphisms in CYP2E1 and GST
Santos, Eliana Abreu; Gonçalves, José Carlos Saraiva; Fleury, Marcos K; Kritski, Afrânio L; Oliveira, Martha M; Velasque, Luciane S; Silva, José Roberto Lapa e; Estrela, Rita de Cássia E.
  • Santos, Eliana Abreu; Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Fármacos e Medicamentos. Rio de Janeiro. BR
  • Gonçalves, José Carlos Saraiva; Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Fármacos e Medicamentos. Rio de Janeiro. BR
  • Fleury, Marcos K; Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas. Rio de Janeiro. BR
  • Kritski, Afrânio L; Universidade Federal do Rio de Janeiro. Instituto de Doenças do Tórax. Rio de Janeiro. BR
  • Oliveira, Martha M; Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro. BR
  • Velasque, Luciane S; Universidade Federal do Estado do Rio de Janeiro. Departamento de Matemática e Estatística. Rio de Janeiro. BR
  • Silva, José Roberto Lapa e; Universidade Federal do Rio de Janeiro. Instituto de Doenças do Tórax. Rio de Janeiro. BR
  • Estrela, Rita de Cássia E; Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Fármacos e Medicamentos. Rio de Janeiro. BR
Braz. j. infect. dis ; 23(6): 381-387, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1089317
ABSTRACT
ABSTRACT

Setting:

Treatment of tuberculosis (TB) can result in Drug-Induced Liver Injury (DILI) since hepatotoxic metabolites are formed during the biotransformation of isoniazid (INH).DILI can be related to the genetic profile of the patient. Single nucleotide polymorphisms in the CYP2E1 gene and GSTM1 and GSTT1 deletion polymorphisms have been associated with adverse events caused by INH.

Objective:

To characterize the genetic polymorphisms of CYP2E1, GSTT1 and GSTM1 in TB carriers.

Design:

This is an observational prospective cohort study of 45 patients undergoing treatment of TB. PCR-RFLP and multiplex-PCR were used.

Results:

The distribution of genotypic frequency in the promoter region (CYP2E1 gene) was 98% wild genotype and 2% heterozygous. Intronic region 78% wild genotype; 20% heterozygous and 2% homozygous variant. GST enzyme genes 24% Null GSTM1 and 22% Null GSTT1. Patients with any variant allele of the CYP2E1 gene were grouped in the statistical analyses.

Conclusion:

Patients with the CYP2E1 variant genotype or Null GSTT1 showed higher risk of presenting DILI (p = 0.09; OR 4.57; 95% CI 0.75-27.6). Individuals with both genotypes had no increased risk compared to individuals with one genotype.
Subject(s)


Full text: Available Index: LILACS (Americas) Main subject: Tuberculosis, Pulmonary / Genetic Predisposition to Disease / Chemical and Drug Induced Liver Injury / Antitubercular Agents Type of study: Observational study / Risk factors Limits: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male Language: English Journal: Braz. j. infect. dis Journal subject: Communicable Diseases Year: 2019 Type: Article Affiliation country: Brazil Institution/Affiliation country: Fundação Oswaldo Cruz/BR / Universidade Federal do Estado do Rio de Janeiro/BR / Universidade Federal do Rio de Janeiro/BR

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Full text: Available Index: LILACS (Americas) Main subject: Tuberculosis, Pulmonary / Genetic Predisposition to Disease / Chemical and Drug Induced Liver Injury / Antitubercular Agents Type of study: Observational study / Risk factors Limits: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male Language: English Journal: Braz. j. infect. dis Journal subject: Communicable Diseases Year: 2019 Type: Article Affiliation country: Brazil Institution/Affiliation country: Fundação Oswaldo Cruz/BR / Universidade Federal do Estado do Rio de Janeiro/BR / Universidade Federal do Rio de Janeiro/BR