Affiliation:
1. Human Genetics Unit, Biological Sciences Division, Indian Statistical Institute, 203 B. T. Road, Kolkata 700108, India.
Abstract
Anti-TB drug (ATD)-related hepatotoxicity is a worldwide serious medical problem among TB patients. Apart from acting on the bacteria, isoniazid, the principal ATD, is also metabolized by human enzymes to generate toxic chemicals that might cause hepatotoxicity. It has been proposed that the production and elimination of the toxic metabolites depends on the activities of several enzymes, such as N-acetyl transferase 2 (NAT2), cytochrome P450 oxidase (CYP2E1) and glutathione S-transferase (GSTM1). There is now evidence that DNA sequence variations or polymorphisms at these loci (NAT2, CYP2E1 and GSTM1) could modulate the activities of these enzymes and, hence, the risk of hepatotoxicity. Since the prevalence of polymorphisms is different in worldwide populations, the risk of ATD hepatotoxicity varies in the populations. Thus, the knowledge of polymorphisms at these loci, prior to medication, may be useful in evaluating risk and controlling ATD hepatotoxicity.
Subject
Pharmacology,Genetics,Molecular Medicine
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