Association of host metabolizing gene profiles with isoniazid and rifampicin resistance phenotypes among tuberculosis patients in Bangladesh

BACKGROUND: Genetic variation in host drug-metabolizing enzymes may influence the pharmacokinetics and treatment response of key anti-tuberculosis (TB) drugs, including isoniazid (INH) and rifampicin (RIF). This study investigated whether selected host metabolic gene profiles were associated with INH and RIF resistance phenotypes among TB patients. METHODS: This prospective study enrolled 41 bacteriologically confirmed TB patients, and blood samples were collected from each of them. Amplification status of six drug-metabolizing genes was assessed using PCR; CYP2E1 genotype was further determined by restriction fragment length polymorphism (RFLP). Associations were evaluated using Fisher's exact test and Firth's penalized logistic regression adjusted for age, sex, and body mass index. Bonferroni correction was applied for multiple testing. RESULTS: None of the investigated host metabolic gene profiles showed statistically significant associations with INH or RIF resistance after adjustment for age, sex, BMI, and Bonferroni correction for multiple testing. Nevertheless, elevated adjusted odds ratios were observed for GSTM1 null genotype, GSTT1/GSTM1 dual-null genotype, and GSTT1 null genotype in relation to INH resistance, and for CYP1A2 absence and GSTT1/CYP1A2 dual-absent genotype in relation to RIF resistance. However, all estimates were accompanied by slightly wide confidence intervals, reflecting substantial uncertainty and limited statistical power. CONCLUSIONS: Exploratory findings suggest that specific host pharmacogenetic profiles may be associated with resistance phenotypes; however, these observations should be considered hypothesis-generating and require validation in larger adequately powered studies.