Source: Annual Congress 2005 - Biological and treatment aspects of tuberculosis
Disease area: Respiratory infections

Abstract

N-acetyltransferase2 (NAT2) is key enzyme of tuberculosis drug of Isoniazide (INH). Tuberculosis patients taking variety of drugs including INH have a risk of hepatotoxicity. Therefore, prediction of INH-induced hepatotoxicity is contributes to prevention of drug-induced adverse effect. Genotyping using a novel oligonucleotide–based DNA microarray for NAT2 polymorphysm is useful for clinical application. In this study, we developed a novel oligonucleotide based DNA microarray for NAT2 genotyping using recently developed technology of attachment of oligonucleotide probes to poly carbodiimido-coated glass slide reported that which could yield stronger hybridization signal and better specificity than the widely used aminosilane slides. To evaluate the validity of the microarray, NAT2 mutation-inserted clones and 42 tuberculosis patient genomes were applied to two methods of the microarray and RFLP. Results of genotyping by these two methods were corresponding. Furthermore, analysis of relationship between NAT2 phenotype determined by DNA-microarray and the risk of INH-induced hepatotoxicity revealed that slow-acetylator has significantly higher risk as previously reported. These findings indicate that this powerful tool is useful for clinical use for prediction of drug adverse effect.


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K. Dobashi, Y. Shimizu, A. Ono, M. Utsugi, T. Kawada, T. Hisada, T. Ishizuka, M. Mori (Maebashi, Japan). DNA-microarray genotyping using oligonucleotide linker of carbodiimides for N-acetyltransferase2 polymorphism on anti-tuberculosis drug-induced hepatotoxicity. Eur Respir J 2005; 26: Suppl. 49, 2896

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