Possible association of rare polymorphism in the ABCB1 gene with rifampin and ethambutol drug-resistant tuberculosis

Abstract

Human P-glycoprotein (P-gp) is a membrane transporter encoded by ABCB1 (also known as MDR1) that plays a critical role in pharmacokinetics of many unrelated drugs. Rifampin (RMP) and ethambutol (ETB), two anti-tubercular agents, are substrates of P-gp. Single nucleotide polymorphisms (SNPs) in ABCB1 have been associated with resistance to several drugs; however, their association with RMP and ETB resistance in tuberculosis patients has not yet been studied. Genotype/allele frequencies in C1236T, G2677T/A and C3435T SNPs of ABCB1 were obtained from 99 tuberculosis patients susceptible or resistant to RMP and ETB (NoRER or RER). 2677G>A allele prevalence was found to be significantly higher in the RER group compared to NoRER (5 resistant vs 2 non-resistant patients, P < 0.01; OR, 11.0; 95% CI, 2.00-56.00). No differences were found in genotype/allele frequencies in C1236T and C3435T SNPs of ABCB1 and resistance to RMP and ETB in tuberculosis patients (P > 0.05). The present study suggests the 2677G>A allele of ABCB1 could be associated with simultaneous resistance to RMP and ETB in pulmonary tuberculosis patients. Further studies with larger sample sizes are needed to confirm this association and explore its nature.

Keywords: Drug-resistant tuberculosis; P-glycoprotein; Polymorphisms; SNPs.