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Clin Sci (Lond). 2017 Jul 5;131(15):1831-1840. doi: 10.1042/CS20170277. Print 2017 Aug 1.

ABCB1 gene polymorphism associated with clinical factors can predict drug-resistant tuberculosis.

Author information

1
Pharmacogenetics Research Laboratory, National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
2
Human Genetic Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
3
Technical Assistance of Clinical Research and Reference Services at National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
4
Clinical Research Laboratory on Mycobacteria, National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
5
Pharmacogenetics Research Laboratory, National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil liane.castro@ini.fiocruz.br.

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.

KEYWORDS:

antibiotic resistance; p-glycoprotein; single nucleotide polymorphisms; tuberculosis-resistant

PMID:
28572401
DOI:
10.1042/CS20170277
[Indexed for MEDLINE]

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