Potencies Of NAT2 Gene As Safety Indicator For Controlling Hepatotoxicity In Tuberculosis-Diabetes Mellitus Treatment: A Preliminary Study

Introduction: Isoniazid (INH) is an anti-tuberculosis drug used widely. It's efficacy in killing Mycobacterium tuberculosis has made this drug as both chemoprophylaxis and first-line therapy in combating tuberculosis (TB). However, irrational dosage of INH may potentiates to isoniazid-induced hepatitis. NA T2 gene is responsible to metabolize INH and change it to the inactive form. In the geneitself, single nucleotide polymorphisms (SNPs) mayappeared, creating changes on itsgenotype, phenotype, andfunctionalactivity on itskinematics. Genotypevariationshave created three phenotypes, namely rapid, intermediate, and slow acetylators. As TB shares comorbiditywith diabetes mellitus (DM), observing this genemight be useful to control progression and potential side effect from TB-DM treatment. This study aimed to analyze the NAT2acetylator status in TB and TB-DM patientsinKupang, Indonesia. Methods: 5 TBand 5 TB-DM patients in Kupang were surveyed. Vein puncture was performed prior to DNA isolation and sequencingto observethe NAT2 sequence. Results: The genotypes of TB patients are NAT2*4/*4 (rapid acetylator), NAT2*4/*6A (intermediate acetylator), and NAT2*13A/*6J (intermediate acetylator). TB-DM patients have NAT2*4/*4, NAT2*4/*5G (intermediate acetylator), NAT2*13A/*6J (intermediate acetylator), NAT2*6A/*6A (slow acetylator) and NAT2*7B/*7B (slow acetylator). Conclusion: NAT2 rapid acetylators may have risk on therapyfailure; slow acetylators may gain risk of INH-induced hepatitis. TBDM patients should be monitored fordouble burden potencies regarding their DM therapy and isoniazid-induced hepatitis. Thus, gene-guided regimen therapy might benefit the patients for more personalized and saferlNH therapy.