Abstract:

Objective: To summarize the mutation characteristics of isoniazid (INH)-resistant strains in terms of drug-resistant gene types, mutation sites and geographical differences, to provide a theoretical basis for the molecular diagnosis of anti-tuberculosis, clinical use of medicines, and the discovery of new drug-resistant genes. Methods: We searched for mutations in INH-resistant genes of Mycobacterium tuberculosis (M.tuberculosis) in China in China Knowledge Network (CNN), Weipu, and Wanfang database with the search terms of “isoniazid resistance” AND “mutation” AND “tuberculosis”, and searched for literature in English with the search terms of “Isoniazid OR INH” AND “mutation” AND “Mycobacterium tuberculosis” AND “China” in PubMed. 145 articles were initially identified, 22 articles were included, 12923 strains were included in the analysis, and 2824 INH-resistant strains were obtained. Taking year 2019 as a time point, the domestic information on INH drug-resistant gene mutations was divided into two parts for studying, then information on drug-resistant gene types, mutation sites, and geographic differences of drug-resistant strains was analyzed in detail. Results: Mutations in INH resistance genes were detected in 96.18% (2716/2824) of strains. The common mutated genes were katG (locus 315), accounting for 74.49% (1965/2638), for which AGC→ACC mutations were predominantly found, accounting for 52.26% (1027/1965). Mutations at locus -15 of the inhA gene were most frequent, accounting for 13.72% (362/2638) with C→T predominating at 89.23% (323/362). fabG1 mutation accounted for 1.97% (52/2638), and the most frequent combined mutation was katG+inhA, accounting for 2.20% (58/2638). Conclusion: Among drug-resistant genes of INH-resistant M.tuberculosis in China, mutations in katG, inhA, and fabG1 gene occured frequently. Mutation loci were dominated by katG315 and inhA15, the most frequent combined mutation was katG+inhA.

Key words: Mycobacterium tuberculosis, Drug resistance, Mutation, Isoniazid