NAT2 Gene rs1041983 is Associated with Anti-Tuberculosis Drug Induced Hepatotoxicity Among Pediatric Tuberculosis in Bandung, Indonesia

Abstract

Background

As pediatric tuberculosis (TB) globally is still reported challenging in diagnosis, to date, a lot of efforts have been established to eliminate the disease including proper treatment regimen using anti-TB drugs. However, antituberculosis drug-induced hepatotoxicity (ADIH) is known to interfere the success of the prescribed therapy. ADIH was found to be correlated with polymorphisms of NAT2 gene, that is responsible to transcript the NAT2 enzyme, a metabolizer of isoniazid (INH). The most common NAT2 gene polymorphisms in Asian population associated with ADIH are rs1041983, rs1799929, rs1799930 and rs1799931. The study aimed to investigate the 4 single nucleotide polymorphisms (SNPs) in pediatric TB that experienced ADIH.

Methods

We conducted a case–control study comparing 31 each of pediatric TB experience with and without ADIH. All pediatric TB was selected from 451 pediatric TB Registry of Respirology Division, Department of Child Health Faculty of Medicine Universitas Padjadjaran/Dr Hasan Sadikin Hospital during January 2016 to July 2018. Genomic DNA PCR and sequencing to identify polymorphisms of rs1041983, rs1799929, rs1799930 and rs1799931 were performed in both groups. Data analysis was performed using the Epi info Ver. 7 software.

Results

Thirty-one pediatric TB experiences with and without ADIH were enrolled in this study. SNP rs1041983 significantly affected the occurrence of ADIH (OR 2.39, CI 95% (1.15–4.96), p=0.019). The rs1799929, rs1799930 and rs1799931 did not significantly affect the occurrence of ADIH (p=0.133, p=0.150 and p=0.659, respectively).

Conclusion

Polymorphism SNP rs1041983 had association with the occurrence of ADIH.

Keywords:

• NAT2 polymorphism
• ADIH
• children

Data Sharing Statement

The software of Bioedit analyzed during the current study is available at https://bioedit.software.informer.com/7.2/ The datasets analyzed during the current study is available from the corresponding author on reasonable request.

Ethics Approval and Consent to Participate

The study was approved in accordance to the requirement of the Ethics Committee Hasan Sadikin Hospital. Written informed consent was obtained from parents of participants in compliance with the Declaration of Helsinki.

Acknowledgment

The authors appreciate the assistance of Fensi Amalina and Erlina Widiarsih from Molecular and Genetic Laboratory Faculty of Medicine Universitas Padjadjaran. We are grateful to participants who participated to this study.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no conflicts of interest for this work.

Additional information

Funding

Funding was provided by Academic Leaderships Grant Program of Universitas Padjadjaran. The funders were not involved in the data analysis or manuscript preparation.