Determining the relation between N-acetyltransferase-2 acetylator phenotype and antituberculosis drug induced hepatitis by molecular biologic tests.
Tuberculosis is treated with a group of drugs that need to be used over a long period of time and isoniazid is the major drug in this group. Antituberculosis drug-induced hepatitis is the most serious problem in tuberculosis treatment. The enzyme N-acetyltransferase-2 (NAT-2) metabolizes isoniazid in the liver so it is considered to cause hepatotoxicity. The association of polymorphic NAT acetylator status and antituberculosis drug-induced hepatitis is discussed. To determine whether acetylator status is a risk factor for antituberculosis drug-induced hepatitis, we genotyped NAT2*5A, NAT2*6A, NAT2*7A/B and NAT2*14A polymorphisms in 100 patients diagnosed with tuberculosis. 70 patients who did not develop hepatotoxicity were classified as the control group, and 30 patients who were diagnosed with antituberculosis drug-induced hepatitis were classified as the study group. NAT2 polymorphisms were divided into three phenotypic groups according to the analytical results obtained. Among the 70 patients constituting the control group; 14 (20%), 37 (52.9%), 19 (27.10%) patients were rapid, intermediate and slow acetylators respectively. In contrast, among the patients constituting the study group; 3 (10%), 4 (13.3%), 23 (76.7%) patients were rapid, intermediate and slow acetylators. The difference was statistically significant when the control and study groups were compared for their acetylator status. The proportion of slow acetylators was much higher in the study group. In conclusion, NAT2 acetylator phenotype analysis by molecular biology methods prior to medical treatment for tuberculosis, can be used both for determining the high-risk group of patients who may develop hepatotoxicity and for closer follow-up during treatment period.
Bozok Cetintaş
Vildan
V
Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey. vildanbcetintas@gmail.com
Erer
Onur Fevzi
OF
Kosova
Buket
B
Ozdemir
Ilker
I
Topçuoğlu
Nejat
N
Aktoğu
Serir
S
Eroğlu
Zuhal
Z
D000107:Acetylation; D000328:Adult; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics*; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014376:Tuberculosis / Q000188:drug therapy*
D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid