NAT2 polymorphism and clinical factors that increase antituberculosis drug-induced hepatotoxicity.

Autor: Mohamed Noor NF; Integrative Pharmacogenomics Institute, Universiti Teknologi MARA, Puncak Alam, Selangor, 42300, Malaysia., Salleh MZ; Integrative Pharmacogenomics Institute, Universiti Teknologi MARA, Puncak Alam, Selangor, 42300, Malaysia.; Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, Selangor, 42300, Malaysia., Mohd Zim MA; Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, 47000, Malaysia., Bakar ZA; Respiratory Medicine Institute, Ministry of Health Malaysia, Kuala Lumpur, 53000, Malaysia., Fakhruzzaman Noorizhab MN; Integrative Pharmacogenomics Institute, Universiti Teknologi MARA, Puncak Alam, Selangor, 42300, Malaysia.; Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, Selangor, 42300, Malaysia., Zakaria NI; Medical Department, Selayang Hospital, Ministry of Health Malaysia, Batu Caves, Selangor, 68100, Malaysia., Lailanor MI; Respiratory Medicine Institute, Ministry of Health Malaysia, Kuala Lumpur, 53000, Malaysia., Teh LK; Integrative Pharmacogenomics Institute, Universiti Teknologi MARA, Puncak Alam, Selangor, 42300, Malaysia.; Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, Selangor, 42300, Malaysia.
Jazyk: angličtina
Zdroj: Pharmacogenomics [Pharmacogenomics] 2022 Jun; Vol. 23 (9), pp. 531-541. Date of Electronic Publication: 2022 May 26.
DOI: 10.2217/pgs-2022-0022
Abstrakt: 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 & 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.
Databáze: MEDLINE
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