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

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 highperformance 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.. RezumatIzoniazida este cel mai intens studiat medicament tuberculostatic din perspectiv farmacogenetic.Cu toate acestea, profilul genotipurilor NAT2 i impactul acestora asupra tratamentului pacienilor cu tuberculoz din Surabaya, Indonezia, nu au fost nc investigate.Scopul acestui studiu a fost de a evalua influena polimorfismelor genei NAT2 asupra nivelurilor plasmatice ale izoniazidei i asupra valorilor enzimelor hepatice (ALT/AST) n timpul fazei intensive a tratamentului anti-TB.n cadrul acestui studiu, 51 de pacieni cu tuberculoz provenind din mai multe centre de sntate comunitare din Surabaya au fost supui recoltrii de probe de snge pentru determinarea valorilor pretratament ale ALT/AST i pentru genotiparea ADN-ului n prima zi de tratament.Nivelurile de izoniazid au fost msurate prin recoltarea probelor de snge la dou ore dup administrarea medicamentului, iar valorile post-tratament ale ALT/AST au fost obinute la sfritul celei de-a doua luni din faza intensiv a tratamentului.Genotiparea ADN-ului a fost realizat prin secveniere de tip Nanopore, utiliznd platforma MinION Mk1B.Analizele ALT/AST au fost efectuate n laboratorul clinic local, iar determinarea nivelurilor de izoniazid s-a realizat prin cromatografie lichid de nalt performan (HPLC).Cele mai frecvente genotipuri NAT2 identificate n acest studiu au fost NAT212A (43,14%), NAT26C (19,61%) i NAT2*12B (13,73%).Majoritatea pacienilor cu tuberculoz din Surabaya au prezentat un fenotip de acetilatori rapizi i niveluri sczute de izoniazid n snge.Totui, nu s-a observat nicio corelaie ntre fenotipul NAT2 i creterea valorilor ALT/AST.n concluzie, polimorfismul genei NAT2 a influenat nivelurile sanguine ale izoniazidei, ns nu a fost corelat cu o cretere a valorilor ALT/AST n timpul fazei intensive a tratamentului tuberculostatic.