NAT2 polymorphism and clinical factors that increased antituberculosis drug-induced hepatotoxicity

Aim: Hepatotoxicity is a known adverse effect of antituberculosis drugs. The NAT2 gene polymorphism has been associated with an increased risk of antituberculosis drug-induced hepatotoxicity (ATDIH). Materials and methods: This study investigates the association of NAT2 polymorphism and clinical risk factors that may contribute to the development of ATDIH. The authors sequenced the NAT2 region of 33 tuberculosis patients who developed ATDIH and 100 tuberculosis patients who did not develop ATDIH during tuberculosis treatment. NAT2 haplotypes were inferred and NAT2 acetylator status was predicted from the combination of the inferred haplotypes. Multiple logistic regression was performed to identify possible factors that are associated with ATDIH. Results: The TT genotype of NAT2*13A and the AA genotype of NAT2*6B were found to be substantially linked with the risk of ATDIH, with odds ratios of 3.09 (95% CI: 1.37-6.95) and 3.07 (95% CI: 1.23-7.69), respectively. NAT2 slow acetylators are 3.39-times more likely to develop ATDIH. Factors that were associated with ATDIH include underlying diabetes mellitus (adjusted odds ratio [AOR] 2.96; 95% CI: 1.05-8.37), pre-treatment serum bilirubin (AOR 1.09; 95% CI: 1.02-1.16) and NAT2 slow acetylator (AOR 3.77; 95% CI: 1.51-9.44). Conclusion: Underlying diabetes mellitus, having a higher baseline bilirubin and being a slow acetylator are identified as the risk factors associated with ATDIH among patients in Malaysia.

Automated summary

This study investigates the association between NAT2 gene polymorphism and the development of antituberculosis drug-induced hepatotoxicity (ATDIH) in Malaysian patients. The TT genotype of NAT2*13A and the AA genotype of NAT2*6B were found to be substantially linked with the risk of ATDIH. Factors such as underlying diabetes mellitus, higher pre-treatment serum bilirubin, and being a NAT2 slow acetylator were also identified as risk factors for ATDIH.