Molecular characterization of the rpoB gene mutations of Mycobacterium tuberculosis isolated from China

Objective: To analyze characterization of the rpoB gene mutations of Mycobacterium tuberculosis isolated from China and to explore the association of specific mutations conferring rifampicin (RIF) resistance with Beijing genotype strains. Methods: Genotypic analysis of 3479 M. tuberculosis isolates including 402 RIF-resistant and 3077 RIF-susceptible isolated from the national drug-resistant tuberculosis baseline survey was performed. Results: DNA sequencing analysis of the 81-bp RIF resistance determining region (RRDR) of the ropB gene revealed that 98.01% of RIF-resistant strains showed rpoB gene mutation, isolates with mutations at codon rpoB531, rpoB526 and rpoB516 were the most frequently. Analysis of the rpoB gene of 3077 RIF-susceptible strains revealed that 98.96% of the strains had no mutation. The distribution of mutation frequency at different critical codons in different regions of China was statistically significant (p = 0.001). There was no significant difference in the occurrence of mutations at critical codons between the rifampicin-resistant Beijing and non-Beijing isolates. Conclusion: About 98% of RIF-resistant strains isolated from China carry mutations in RRDR of rpoB gene. Mutation profiles in RIF-resistant M. tuberculosis clinical isolates are variable depending on the different geographical regions of China. The results provide valuable information in adopting new molecular methods for diagnosis of TB in China.