The role of cigarette smoking and liver enzymes polymorphisms in anti-tuberculosis drug-induced hepatotoxicity in Brazilian patients
| Autor: | Marcel de Souza Borges Quintana, Leonardo A. Rosadas, S. P. Monteiro, Liane de Castro, Kênia B. El-Jaick, Camila Zaverucha-do-Valle, M. J. M. Costa |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Microbiology (medical) Heterozygote medicine.medical_specialty Tuberculosis Arylamine N-Acetyltransferase Immunology Antitubercular Agents Pharmacology Polymerase Chain Reaction Microbiology Gastroenterology law.invention Cigarette smoking Risk Factors law Liver enzyme Internal medicine Genotype medicine Cytochrome P-450 CYP3A Humans Genetic Predisposition to Disease Polymerase chain reaction Retrospective Studies Polymorphism Genetic CYP3A4 business.industry Homozygote Smoking Cytochrome P-450 CYP2E1 CYP2E1 medicine.disease Phenotype Infectious Diseases Case-Control Studies Female Chemical and Drug Induced Liver Injury Restriction fragment length polymorphism business Polymorphism Restriction Fragment Length |
| Zdroj: | Tuberculosis. 94:299-305 |
| ISSN: | 1472-9792 |
| DOI: | 10.1016/j.tube.2014.03.006 |
| Popis: | Tuberculosis (TB) is still a major health concern and side-effects related to the treatment, especially drug-induced 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 slow acetylators (OR: 0.34, CI 95: 0.16-0.71; 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: 0.11-0.64; 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. |
| Databáze: | OpenAIRE |
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