https://orcid.org/0000-0003-1520-9598
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ABSTRACT
Background
Single nucleotide polymorphisms (SNPs) in the N-acetyltransferase 2 (NAT2) gene as well as several other clinical factors can contribute to the elevation of liver function test values in tuberculosis (TB) patients receiving antitubercular therapy (ATT).
Research design and methods
A prospective study involving dynamic monitoring of the liver function tests among 130 TB patients from baseline to 98 days post ATT initiation was undertaken to assess the influence of pharmacogenomic and clinical variables on the elevation of liver function test values. Genomic DNA was extracted from serum samples for the assessment of NAT2 SNPs. Further, within this study population, we conducted a case control study to identify the odds of developing ATT-induced drug-induced liver injury (DILI) based on NAT2 SNPs, genotype and phenotype, and clinical variables.
Results
NAT2 slow acetylators had higher mean [90%CI] liver function test values for 8–28 days post ATT and higher odds of developing DILI (OR: 2.73, 90%CI: 1.05–7.09) than intermediate acetylators/rapid acetylators.
Conclusion
The current study findings provide evidence for closer monitoring among TB patients with specific NAT2 SNPs, genotype and phenotype, and clinical variables, particularly between the period of more than a week to one-month post ATT initiation for better treatment outcomes.
Declaration of interests
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/17512433.2024.2311314
Ethics statement
The study had received institutional ethics committee approval (Kasturba Hospital and Kasturba Medical College IEC No. 243/2019), and informed consent was obtained for all patients.
Author contributions
M Rao was involved in funding acquisition for the project. M Rao, L Thomas, and AP Raju were involved in the conceptualization of the study. Chaithra was involved in patient recruitment, data collection and sample processing. Chaithra and L Thomas were involved in data curation. L Thomas, S Kulavalli, and M Rao were involved in laboratory experiments. Analysis and interpretation of data were done by AP Raju and L Thomas. L Thomas wrote the first draft of the paper. AP Raju, Chaithra, M Varma, CS SV, M Banerjee, K Saravu, S Mallayasamy and M Rao critically revised the manuscript. All authors have read and approved the final manuscript.
Acknowledgments
L Thomas thanks the Indian Council of Medical Research for providing Senior Research Fellowship (No.45/25/2020/PHA/BMS) and contingency grant from Manipal Academy of Higher Education (MAHE). AP Raju and S Kulavalli are thankful to the Dr. TMA Pai PhD scholarship from MAHE. Chaithra is thankful to the Junior Research Fellowship from ICMR (F.No.5/8/5/45/multicentric study/2019/ECD-1). M Rao is also thankful to the Department of Science & Technology- Fund for Improvement of S&T Infrastructure in Universities and Higher Educational Institutions (DST-FIST) (TPN: 32196) for providing Quant 5 Studio real time PCR (Applied Biosystems, USA).
Data availability statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.