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Peer-reviewedCC BY-NC-NDJournal of thoracic disease

The effects of Mycobacterium tuberculosis genotypes on clinical phenotypes revealed by whole-genome sequencing technology in China.

  • Wei Huang1,2
  • Jialei Liang3
  • Mingquan Guo4
  • Xuhui Liu1
  • Bo Yan5
  • Qian Gao3
  • Yinzhong Shen6
6 affiliations
  1. 1Department of Tuberculosis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  2. 2Department of Pulmonary and Critical Care Medicine, Shanghai Geriatric Medical Center, Shanghai, China.
  3. 3Shanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Science, Fudan University, Shanghai, China.
  4. 4Department of Laboratory Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  5. 5Center for Tuberculosis Research, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
  6. 6Department of Infection and Immunity, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
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Abstract

Findings related to the associations between Mycobacterium tuberculosis (MTB) lineages and tuberculosis (TB) clinical phenotypes remain inconsistent across studies, primarily because conventional genotyping techniques lack the resolution to distinguish fine-scale sublineages. This study aimed to rigorously verify the clinical characteristics and prognostic significance of predominant Beijing-lineage strains circulating in China using high-resolution genomic evidence. In total, 173 patients with TB were enrolled in the study, and whole-genome sequencing (WGS) was performed on 213 clinical MTB isolates; mixed-strain infections were excluded from subsequent analyses. Phylogenetic sublineage classification was performed based on single-nucleotide polymorphism (SNP) profiling. Multivariate logistic regression was used to independently assess the associations between MTB genotypes, clinical manifestations, and treatment outcomes, after adjusting for demographic and clinical confounding factors. Among the 172 valid isolates, 80.8% were classified as East Asian Beijing lineage (lineage 2), 18.0% as Euro-American lineage (lineage 4), and 1.2% as Indo-Oceanic lineage (lineage 1). Compared with the non-Beijing strains, the Beijing strains were independently associated with an increased risk of pulmonary cavitation [adjusted odds ratio (aOR) =4.76, 95% confidence interval (CI): 2.01-11.26, P=0.006], as well as a decreased risk of disseminated TB (aOR =0.40, 95% CI: 0.17-0.95, P=0.04). No significant association was observed between the Beijing genotype and treatment failure, whereas cavitary disease was an independent predictor of treatment failure. MTB genetic diversity contributes substantially to heterogeneity in TB clinical phenotypes. WGS enables precise sublineage identification and facilitates robust genotype-phenotype analysis. These findings support the implementation of genomic surveillance to optimize individualized clinical management and inform targeted TB prevention strategies in endemic regions.

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Cite

BibTeXRIS
BibTeX
@article{huang2026effects,
  title = {{The effects of Mycobacterium tuberculosis genotypes on clinical phenotypes revealed by whole-genome sequencing technology in China.}},
  author = {Wei Huang and Jialei Liang and Mingquan Guo and Xuhui Liu and Bo Yan and Qian Gao and Yinzhong Shen},
  journal = {Journal of thoracic disease},
  year = {2026},
  month = oct,
  doi = {10.21037/jtd-2026-2825},
  url = {https://europepmc.org/article/MED/42996653},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - The effects of Mycobacterium tuberculosis genotypes on clinical phenotypes revealed by whole-genome sequencing technology in China.
AU  - Wei Huang
AU  - Jialei Liang
AU  - Mingquan Guo
AU  - Xuhui Liu
AU  - Bo Yan
AU  - Qian Gao
AU  - Yinzhong Shen
PY  - 2026
DA  - 2026/10/22
JO  - Journal of thoracic disease
DO  - 10.21037/jtd-2026-2825
UR  - https://europepmc.org/article/MED/42996653
AB  - Findings related to the associations between Mycobacterium tuberculosis (MTB) lineages and tuberculosis (TB) clinical phenotypes remain inconsistent across studies, primarily because conventional genotyping techniques lack the resolution to distinguish fine-scale sublineages. This study aimed to rigorously verify the clinical characteristics and prognostic significance of predominant Beijing-lineage strains circulating in China using high-resolution genomic evidence. In total, 173 patients with TB were enrolled in the study, and whole-genome sequencing (WGS) was performed on 213 clinical MTB isolates; mixed-strain infections were excluded from subsequent analyses. Phylogenetic sublineage classification was performed based on single-nucleotide polymorphism (SNP) profiling. Multivariate logistic regression was used to independently assess the associations between MTB genotypes, clinical manifestations, and treatment outcomes, after adjusting for demographic and clinical confounding factors. Among the 172 valid isolates, 80.8% were classified as East Asian Beijing lineage (lineage 2), 18.0% as Euro-American lineage (lineage 4), and 1.2% as Indo-Oceanic lineage (lineage 1). Compared with the non-Beijing strains, the Beijing strains were independently associated with an increased risk of pulmonary cavitation [adjusted odds ratio (aOR) =4.76, 95% confidence interval (CI): 2.01-11.26, P=0.006], as well as a decreased risk of disseminated TB (aOR =0.40, 95% CI: 0.17-0.95, P=0.04). No significant association was observed between the Beijing genotype and treatment failure, whereas cavitary disease was an independent predictor of treatment failure. MTB genetic diversity contributes substantially to heterogeneity in TB clinical phenotypes. WGS enables precise sublineage identification and facilitates robust genotype-phenotype analysis. These findings support the implementation of genomic surveillance to optimize individualized clinical management and inform targeted TB prevention strategies in endemic regions.
SN  - 2072-1439
SN  - 2077-6624
ER  -