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THE IMPACT OF NAT2 POLYMORPHISM ON ISONIAZID BLOOD LEVELS AND LIVER ENZYME ELEVATION IN TUBERCULOSIS PATIENTS IN SURABAYA, INDONESIA

DIAN NATASYA RAHARDJO 1,2, MARIANA WAHJUDI 3, RATU AYU DEWI SARTIKA 4, JONATHAN JONATHAN 3, DHAMMIKO WONGGO 3, RETNOSARI ANDRAJATI 1*

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Isoniazid is the most pharmacogenetically studied anti-tuberculosis (TB) drug. However, the NAT2 genotype profile and its impact on the treatment of TB patients in Surabaya, Indonesia, have not yet been discovered. The objective of this study was to examine the impact of NAT2 polymorphisms on isoniazid blood levels and liver enzymes (ALT/AST) during the intensive phase of TB treatment. In this cohort study, 51 TB patients from several Community Health Centres in Surabaya underwent blood sampling for pre-ALT/AST and DNA genotyping examinations on the first day of treatment. Isoniazid levels were measured by taking blood samples 2 hours after the drug administration, and post-ALT/AST values were obtained at the end of the 2nd month of the intensive phase of TB treatment. Nanopore sequencing was employed to genotype DNA using MinION Mk1B. ALT/AST exams were performed with the local clinical laboratory, and isoniazid levels were measured using high- performance liquid chromatography (HPLC). The predominant NAT2 genotypes observed in this study were NAT2*12A (43.14%), NAT2*6C (19.61%), and NAT2*12B (13.73%). Most TB patients in Surabaya possessed rapid acetylator phenotypes and low isoniazid blood levels. However, no correlation was observed between the NAT2 phenotype and the elevation of ALT/AST. In conclusion, NAT2 polymorphism influences the isoniazid blood levels but does not correlate with elevated ALT/AST following the intensive phase of TB treatment..