Association of N-acetyltransferase-2 genotypes and anti-tuberculosis induced liver injury; first case-controlled study from Iran.
OBJECTIVE
The goals of this study were to identify the frequency of N-acetyltransferase-2 genotypes and phenotypes in Iranian tuberculosis and healthy subjects and to evaluate correlation of acetylator phenotype and antituberculosis-induced hepatotoxicity in pulmonary tuberculosis patients.


METHODS
A total of 50 newly diagnosed pulmonary tuberculosis patients and 50 healthy Iranian subjects were enrolled in the study. A combination of polymerase chain reaction and restriction fragment length polymorphism were used to investigate N-acetyltransferase-2 alleles. The tuberculosis patients were followed for occurrence of antituberculosis induced hepatotoxicity during the treatment course. Correlation between N-acetyltransferase-2 phenotypes and antituberculosis induced hepatotoxicity was evaluated.


RESULTS
Frequency of slow, intermediate and fast acetylator genotypes in the healthy group were 32%, 54% and 14% and in the tuberculosis patients were 28%, 64% and 8%, respectively. Hepatotoxicity was detected in 64.3% of slow acetylators, 15.6% of intermediate acetylators and interestingly in none of the fast acetylators.


CONCLUSIONS
There were no significant difference in distribution of various N-acetyltransferase-2 alleles, genotypes and phenotypes between pulmonary TB patients and healthy individuals. Among patients, anti-tuberculosis induced hepatotoxicity was more frequent in slow acetylators in comparison with fast acetylators in Iranian tuberculosis patients.
Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. khalilih@sina.tums.ac.ir
Hossein
H
Khalili
Shamileh
S
Fouladdel
Mohammad
M
Sistanizad
Mahboobeh
M
Hajiabdolbaghi
Ebrahim
E
Azizi
D000107:Acetylation / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000009:adverse effects*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014397:Tuberculosis, Pulmonary / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human