Increased risk of antituberculosis drug-induced hepatotoxicity in individuals with glutathione S-transferase M1 'null' mutation

Majumder, Partha P. ; Roy, Bidyut ; Chowdhury, Abhijit ; Kundu, Somnath ; Santra, Amal ; Dey, Badal ; Chakraborty, Madan (2001) Increased risk of antituberculosis drug-induced hepatotoxicity in individuals with glutathione S-transferase M1 'null' mutation Journal of Gastroenterology and Hepatology, 16 (9). pp. 1033-1037. ISSN 0815-9319

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Official URL: http://onlinelibrary.wiley.com/doi/10.1046/j.1440-...

Related URL: http://dx.doi.org/10.1046/j.1440-1746.2001.02585.x

Abstract

Background: Pathogenesis and genetic factors influencing predisposition to antituberculosis drug (ATD)-induced hepatotoxicity are not clear. Polymorphism at the genetic locus of a drug and xenobiotic compound metabolizing enzyme, N-acetyltransferase type 2 (NAT2), is reported to be associated with the excess generation of toxic reactive metabolites. Polymorphisms at the glutathione S-transferase (GST) loci (GSTM1 and GSTT1) are involved in the detoxification of these toxic metabolites in the human body to a lesser extent. We have examined whether polymorphisms at these loci are associated with the risk of ATD-induced hepatotoxicity. Methods: In this case-control study, 33 pulmonary tuberculosis patients with ATD-induced hepatotoxicity and 33 pulmonary tuberculosis patients receiving ATD drugs without any evidence of hepatotoxicity were considered as cases and controls, respectively. Point mutations at NAT2 and homozygous 'null' mutations at GSTM1 and GSTT1 genes were looked into genomic DNA, isolated from peripheral blood mononuclear cells by using polymerase chain reaction (PCR). Results: The frequency of homozygous 'null' mutation at the GSTM1 gene was significantly higher among cases (n = 17, 52%) than controls (n = 8, 24%) (P <0.05, relative risk 2.13, 95% CI: 1.25-3.10). Frequencies of mutations at GSTT1 and NAT2 genes did not differ significantly between cases and controls.

Item Type:Article
Source:Copyright of this article belongs to John Wiley and Sons, Inc.
Keywords:Antituberculosis Drug-induced Hepatotoxicity; Genetic Susceptibility; Glutathione S-transferase M1; Glutathione S-transferase T1; N-acetyltransferase Type 2; Polymorphism
ID Code:21299
Deposited On:20 Nov 2010 13:09
Last Modified:06 Jun 2011 07:43

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