, , and genetic polymorphisms and their associations with susceptibility to antituberculosis drug-induced liver injury in Thai tuberculosis patients.

Antituberculosis drug-induced liver injury (ATDILI) is the common adverse reaction of antituberculosis drugs. Glutathione S-transferases (GSTs), which are phase II metabolizing enzymes for detoxification, are recognized as potential mediators of hepatotoxicity. However, role of s polymorphisms in ATDILI pathogenesis has never been observed in Thais. This study aimed to investigate associations between s and ATDILI susceptibility. This retrospective case-control multicentered study was conducted by the collaboration from ten secondary and tertiary care hospitals across Thailand, including Northern, Central, and Southern parts of Thailand. We enrolled 80 tuberculosis (TB) patients with ATDILI and 174 those without ATDILI into the study. Polymerase chain reaction (PCR) was used to determine genetic polymorphisms of and genes. genotyping data were derived from microarray data. We illustrated that null and / dual null genotypes were correlated with an increased risk of ATDILI with odds ratio (OR) at 1.83 (95% confidence interval (CI), 1.00 to 3.35; P = 0.049) and 2.12 (95%CI, 1.02 to 4.38; P = 0.044), respectively. Interestingly, null and / dual null genotypes were found to be correlated with an increased risk of ATDILI in Thai TB patients who carried wild type phenotype with OR 2.99 (95%CI, 1.07 to 8.39; P = 0.037) and 3.44 (95%CI, 1.01 to 11.71; P = 0.048), respectively. Collectively, null and / dual null genotypes were associated with a higher risk of ATDILI in Thai TB patients, which may serve as alternative genetic biomarkers for ATDILI.