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Resistance to isoniazid (INH), which is one of the most important drugs in Mycobacterium tuberculosis chemotherapy, has been associated with mutations in genes encoding the mycobacterial catalse-peroxidase (katG), the enoy1 acy1 carrier protein (ACP) reductase (inhA), alky1 hydroperoxide reductase (ahpC, beta-ketoacy1 acy1 carrier protein synthase (kasA), and NADH dehydrogenase (ndh). In this study, we examined INH-resistance related genes in 50 INH-resistant and 24 INH-susceptible isolates by PCR-sequence analysis. In brief, mutations at the katG gene were found at codon 315 alone (2/50), at codon 463 alone (19/50), and both at 315 and 463 (29/50). However, while mutations at codon 315 were only detected in INH-resistant isolates, mutations at codon 463 were also detected in INH-susceptible isolates indicating mutations at 463 alone do not seem to confer resistance to INH. Similar to the case of fore 463, some of inhA mutations were also found among INH-susceptible isolates. For example, whereas mutations at 8 upstream of the start codon (UPS) and 15 UPS of the inhA gene were detected only in INH-resistant isolates, mutations at 101, 115, and 125 UPS were detected only in INH-susceptible isolates. Many different kinds of mutations were detected in INH-resistant isolates at ohpC, oxy<sup>R</sup> gene, and intergenic region of the oxy<sup>R</sup>-ahp<sup>C</sup> genes. However, the mutations were not faund oxy<sup>R</sup> and the intergenic regions in INH-susceptible isolates. No mutations were found at either kasA at ndh gene among INH-resistant isolates. In conclusion, some of mutations such as katG 315, inhA promoter region, and oxy<sup>R</sup>-ahp<sup>C</sup> seem to be strongly related to INH-resistance. Currently we are developing a molecular diagnostic method based on these results.

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UCI(KEPA) : I410-ECN-0101-2009-510-017356841