Author | Pontual, Yasmin | |
Author | Pacheco, Vanessa S. S. | |
Author | Monteiro, Sérgio P. | |
Author | Quintana, Marcel S. B. | |
Author | Costa, Marli J. M. | |
Author | Rolla, Valeria C. | |
Author | Castro, Liane de | |
Access date | 2018-06-19T16:01:00Z | |
Available date | 2018-06-19T16:01:00Z | |
Document date | 2017 | |
Citation | PONTUAL, Yasmin et al. ABCB1 gene polymorphism associated with clinical factors can predict drug-resistant tuberculosis. Clinical Science, v. 131, p. 1831–1840, 2017. | pt_BR |
ISSN | 0143-5221 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/26963 | |
Language | eng | pt_BR |
Publisher | Portland Press | pt_BR |
Rights | restricted access | pt_BR |
Subject in Portuguese | Tuberculose | pt_BR |
Subject in Portuguese | Polimorfismo do gene ABCB1 | pt_BR |
Subject in Portuguese | Fatores clínicos | pt_BR |
Subject in Portuguese | Resistência a medicamentos | pt_BR |
Title | ABCB1 gene polymorphism associated with clinical factors can predict drug-resistant tuberculosis | pt_BR |
Type | Article | pt_BR |
DOI | 10.1042/CS20170277 | |
Abstract | Polymorphism in the ABCB1 gene encoding P-glycoprotein, a transmembrane drug efflux pump, contributes to drug resistance and has been widely studied. However, their association with rifampicin and ethambutol resistance in tuberculosis (TB) patients is still unclear. Genotype/allele/haplotype frequencies in c.1236C > T (rs1128503), c.2677G > T/A (rs2032582), and c.3435C > T (rs1045642) were obtained from 218 patients. Of these, 80 patients with rifampicin and/or ethambutol resistance were selected as the case group and 138 patients were selected for the control group through the results of their culture and drug-sensitive tests. Patients aged <18 years and HIV-positive serologic tests were excluded. ABCB1 polymorphisms were determined using a PCR direct-sequencing approach, and restriction fragment length polymorphism (RFLP). A nomogram was constructed to simulate a combined prediction of the probability of anti-TB drug resistance, with factors including genotype c.1236C > T (rs1128503) (P=0.02), clinical form (P=0.03), previous treatment (P=0.01), and skin color (P=0.03), contributing up to 90% chance of developing anti-TB drug resistance. Considering genotype analyses, CT (rs1128503) demonstrated an increased chance of anti-TB drug resistance (odds ratio (OR): 2.34, P=0.02), while the analyses for ethambutol resistance revealed an association with a rare A allele (rs2032582) (OR: 12.91, P=0.01), the haplotype TTC (OR: 5.83, P=0.05), and any haplotype containing the rare A allele (OR: 7.17, P=0.04). ABCB1 gene polymorphisms in association with others risk factors contribute to anti-TB drug resistance, mainly ethambutol. The use of the nomogram described in the present study could contribute to clinical decision-making prior to starting TB treatment. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Assistência Técnica de Pesquisa Clínica. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Micobactérias. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Micobactérias. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ. Brasil. | pt_BR |
Subject | ABCB1 gene polymorphism | pt_BR |
Subject | Polymorphism | pt_BR |
Subject | Drug-resistant tuberculosis | pt_BR |
Subject | Clinical factors | pt_BR |
e-ISSN | 1470-8736 | |
Embargo date | 2030-01-01 | |