AbstrakTuberkulosis (TB) masih menjadi masalah kesehatan utama di Indonesia. Enzim N-asetil- transferase 2 (NAT2) telah diketahui memainkan peranan penting dalam proses metabolism obat anti tuberkulosis, terutama Isoniazid. Polimorfisme NAT2 dilaporkan memiliki asosiasi dengan resiko toksisitas obat dan perkembangan berbagai penyakit. Anti-TuberculosisDrug- induced liver injury (AT-DILI) merupakan efek samping yang biasanya terjadi pada pen- gobatan tuberkulosis. Beberapa penelitian menunjukkan bahwa pasien dengan fenotipe aset- ilator NAT2 lambat sangat rentan terhadap perkembangan AT-DILI. Penelitian kami sebe- lumnya menunjukkan bahwa frekuensi asetilator NAT2 lambat di Indonesia cukup tinggi, pada etnis Jawa-sunda sebesar 33% dan pada etnis Melayu 38%. Oleh karena itu, kesadaran masyarakat terhadap kerentanan AT-DILI harus di tingkatkan. Penelitian kami terbaru menunjukkan bahwa NAT2*6A, yang merupakan alel asetilator lambat, memiliki asosiasi yang signifikan terhadap AT-DILI (p=7.7×10−4, odds ratio (OR)=4.75 (1.8–12.55)). Selain itu, pasien dengan fenotipe asetilator lambat menunjukkan risiko AT-DILI lebih tinggi dibandingkan pasien dengan fenotipe cepat atau intermediet (p = 1,7 × 10-4, OR = 3,45 (1,79-6,67)). Farmakogenomik merupakan suatu studi variasi ekspresi gen individu terkait kerentanan terhadap penyakit dan respon terhadap obat baik pada individu itu sendiri mau- pun pada populasi. Penelitian dan penerapan farmakogenomik dapat membantu menentukan pengobatan yang terbaik untuk pasien dan memiliki peluang keberhasilan yang lebih tinggi. Oleh karena itu, kita perlu mendorong pengembangan penelitian farmakogenomik, mengusulkan kolaborasi baik secara nasional maupun internasional dan membuat masyarakat Indonesia menyadari betapa pentingnya penerapan farmakogenomik dalam kehidupan mereka.Kata kunci: NAT2, Asetilator lambat, AT-DILI, Farmakogenomik AbstractTuberculosis (TB) is still remains as a major health problem in Indonesia. The enzyme N- Acetyltransferase 2 (NAT2) has been known to play an important role in metabolizing anti- tuberculosis drugs, especially isoniazid. Polymorphisms of NAT2 are reportedly associated with the risk of drug toxicities and development of various diseases. Anti-Tuberculosis Drug-induced liver injury (AT-DILI) is the most common adverse drug reaction in the treatment of tuberculosis (TB). Several studies showed that a patient with slow acetylator phenotype has a high susceptibility to AT-DILI. Our research on the Indonesian population, in Javanese and Sundanese dan Malay ethnics showed 33% and 38% NAT2 slow acetylator phenotype, respectively. Therefore, Indonesia populations have to be aware with the development of AT-DILI. Our recent study showed thatNAT2*6A as a slow acetylator allele was signifi- cantly associated with AT-DILI (P=7.7×10−4, odds ratio (OR)=4.75 (1.8–12.55)). Addi- tionally, patients with slow acetylator phenotype showed higher risk of AT-DILI than pa- tients with the rapid acetylator or intermediate acetylator phenotypes (P=1.7×10−4,OR=3.45 (1.79–6.67)). Pharmacogenomics is a study of the variation of in- dividual gene expression related to susceptibility to disease and response to drugs both in the individual itself and population. Pharmacogenomics research and implementation can help to select the best therapeutic option for patients suffering from certain diseases that are both cost effective and having higher chance of success. Therefore, we need to foster phar- macogenomics research development, propose collaboration both nationally and interna- tionally and make the Indonesia society realize how important pharmacogenomics imple- mentation is in their life.Keywords: NAT2, Slow acetylator, AT-DILI, Pharmacogenomics
Chromosomal localization of human genes for arylamine N-acetyltransferase
