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

Achmad Headriawan; Alvinsyah Adhityo Pramono; Abdurachman Sukadi; Alex Chairulfatah; Ani Melani Maskoen; Heda Melinda Nataprawira

doi:10.2147/TACG.S303668

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

Appl Clin Genet. 2021 Jun 3:14:297-303. doi: 10.2147/TACG.S303668. eCollection 2021.

Authors

Achmad Headriawan¹, Alvinsyah Adhityo Pramono², Abdurachman Sukadi¹, Alex Chairulfatah¹, Ani Melani Maskoen^{2

3}, Heda Melinda Nataprawira¹

Affiliations

¹ Department of Child Health.
² Research Center of Medical Genetics.
³ Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital, 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: ADIH; NAT2 polymorphism; children.

Grants and funding

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