Associations between host efflux pump gene polymorphisms (ABCB1, ABCC1, ABCG2) and drug-resistant tuberculosis in a Chinese cohort.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is associated with alterations in drug pharmacokinetics (PK), aberrant expression of efflux pump transporters, and genetic mutations. Polymorphisms in host genes encoding efflux pumps may affect drug concentrations, potentially contributing to the emergence of drug resistance. This study aims to investigate the association between single nucleotide polymorphisms (SNPs) in host efflux pump transporter genes and the development of drug resistance in tuberculosis.

METHODS: This study enrolled 117 DR-TB patients, 193 patients with drug-sensitive tuberculosis (DS-TB) and 398 healthy control subjects (HCS). SNPs associated with drug resistance were selected based a comprehensive literature review and publicly available databases. A total of 12 SNPs within four ABC transporter genes were selected and genotyped: ABCB1 (rs1128503, rs2032582, rs3842, rs1045642); ABCC1 (rs212091, rs3743527); ABCC2 (rs717620, rs2273697, rs3740066, rs8187710); and ABCG2 (rs2231142, rs2231137). The relationship between SNPs and phenotype was evaluated using logistic regression analysis, with adjustments for potential confounding factors including sex, age and ethnicity.

RESULTS: All 12 SNPs were in Hardy-Weinberg genetic equilibrium (P > 0.5). Genetic analysis revealed statistically significant associations between efflux pump gene polymorphisms and distinct drug-resistant tuberculosis profiles. Specifically, the ABCC1 rs212091 CC genotype was significantly associated with an increased risk of both overall drug-resistant TB (OR = 4.84, 95 % CI: 1.24-18.92) and multidrug-resistant TB (OR = 8.45, 95 % CI: 1.50-47.65). In contrast, the ABCB1 rs3842 CC genotype demonstrated a protective effect against MDR-TB (OR = 0.37, 95 % CI: 0.14-0.99), whereas the ABCG2 rs2231142 TT genotype was linked to a decreased risk of pre-extensively drug-resistant TB (OR = 0.41, 95 % CI: 0.17-0.97).

CONCLUSION: Our findings suggest that polymorphisms in host efflux pump genes may affect susceptibility to different DR-TB phenotypes. The identified risk (ABCC1 rs212091) and protective variants (ABCB1 rs3842, ABCG2 rs2231142) reveal genetic mechanisms underlying drug resistance. Further validation in larger, more diverse populations is needed.