Study of NAT2 Gene Polymorphisms in an Indian Population

Abstract

The results suggested high variation in the frequencies of NAT2 alleles and genotypes within Indian populations, which influence plasma isoniazid concentrations. Further studies of the relationship between NAT2 genotypes and adverse drug events are required to make genotyping a helpful tool for optimizing the isoniazid therapeutic response and minimizing adverse drug reactions, particularly in countries with a high burden of tuberculosis.

N-acetyltransferase gene polymorphisms & plasma isoniazid concentrations in patients with tuberculosis

“…Although there appeared to be a trend in the proportion of patients with sub-therapeutic INH concentrations, the differences were not significant. The drug concentrations observed in our study was higher than that reported from an earlier study from Mumbai, which could be because of differences in the INH dose used in these studies, 600 mg in the present study and 300 mg in the Mumbai study5.…”

“…Several studies to date have documented the influence of NAT2 genotypes on plasma concentrations of INH251415. Drug-induced hepatotoxicity as well as adverse drug events have also been reported16.…”

“…The sample size was calculated based on the study of Singh et al 5, which reported mean (95% confidence interval) two-hour plasma INH concentration of 2.4 μg/ml (1.5-3.4 μg/ml) in fast acetylators and 5.6 μg/ml (4.8-6.4 μg/ml) in slow acetylators. With 95 per cent confidence level, 90 per cent power and assuming the expected true difference to be 1 μg/ml, the sample size was calculated as 323.…”

“…Singh et al 5 have shown high variation in NAT2 gene frequencies from different regions in India. Zabost et al 6 explored the relationship between NAT2 genotypes and serum concentrations of INH in a Polish population and concluded that determining mutations in the NAT2 gene enabled the identification of the INH acetylator type in patients, and the genotyping results were consistent with the phenotype.…”

Human pharmacogenetic pecularities affecting the action of anti-tuberculosis medicines

“…[7,23]. On the other hand, the NAT2 polymorhism affects the rate of inactivation and, therefore, the concentration in blood of certain medicines, including antituberculosis drug isoniazid [34]. Thus, determination of the genotype/phenotype of NAT2 can serve as a supplementary method for improving the pharmacotherapy efficiency and minimization of side effects during treatment of certain diseases, for instance tuberculosis (TB).…”