Association of N-Acetyltransferase-2 Genotypes and Anti-Tuberculosis Induced Liver Injury: First Case-Controlled Study from Iran

Hossein      Khalili; Shamileh      Fouladdel; Mohammad      Sistanizad; Mahboobeh      Hajiabdolbaghi; Ebrahim      Azizi

doi:10.2174/157488611794479946

Abstract

Purpose: 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. Method: 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. Conclusion: 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.

Keywords: NAT-2 genotypes, anti-tuberculosis, hepatotoxicity, phenotypes, INH, WHO, HIV, liver function tests, ALT, AST, Sampling, EDTA, DNA, Statistical Analysis, Alleles