CYP2E1 POLYMORPHISMS AND SUSCEPTIBILITY TO ANTI-TUBERCULOSIS DRUG-INDUCED HEPATOTOXICITY IN INDONESIA POPULATION
DOI:
https://doi.org/10.31004/prepotif.v9i1.41251Keywords:
Tuberkulosis, polimorfisme CYP2E1, hepatotoksisitas yang diinduksi oleh obat.Abstract
Pengobatan Tuberkulosis (TB), berdasarkan penggunaan isoniazid (INH), rifampisin (RMP) dan pirazinamid (PZA), terbukti menyebabkan hepatotoksisitas yang diinduksi oleh obat (Drug Induced Hepatotoxicity/DIH). Penelitian terbaru menunjukkan bahwa variasi genetik dapat dikaitkan dengan risiko DIH, seperti status asetilator INH, yang terkait dengan polimorfisme N-asetil transferase (NAT) 2, yang mana asetilator lambat pada umumnya lebih rentan terhadap efek samping obat. Proporsi asetilator cepat dan lambat sangat bervariasi pada populasi dengan etnis atau geografis yang berbeda yang telah dijelaskan dalam berbagai penelitian, tetapi, masih ada informasi yang terbatas dalam populasi kita. Tujuan dari penelitian ini adalah untuk menyelidiki kontribusi polimorfisme CYP2E1 terhadap DIH anti-TB pada populasi kami. Penelitian kasus kontrol ini dilakukan di Rumah Sakit Cipto Mangunkusumo, Jakarta dan Rumah Sakit Omni Alam Sutera, Tangerang, Indonesia dari Januari 2015 - Desember 2016. Kami merekrut 35 orang dengan DIH dan 34 orang tanpa DIH. Profil fungsi hati lengkap, bilirubin total serum, bilirubin tidak langsung, dan bilirubin langsung diukur. Kami melakukan genotipe polimorfisme CYP2E1 rs3813867, rs2031920 dan rs6413432. Kami menemukan bahwa polimorfisme CYP2E1 c1/c1 (tipe liar homozigot) pada 61 subjek (88,4%) dan tidak ada perbedaan yang signifikan secara statistik antara tipe liar homozigot dan varian yang jarang (mutan alel) dalam kejadian DIH (95% CI 0,403 - 8,383, P = 0,338). Kami mengusulkan bahwa polimorfisme CYP2E1 tidak dapat membantu dalam memprediksi kerentanan terhadap hepatotoksisitas yang diinduksi oleh obat anti-tuberkulosis pada populasi di Indonesia.References
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