Investigation of Matrix Metalloproteinase–Related Genetic Variations Associated With Cavity Formation in Pulmonary Tuberculosis
5 affiliations
- 1Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea .
- 2Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea .
- 3Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea .
- 4Veterans Health Service Medical Research Institute, Veterans Health Service Medical Center, Seoul, Korea .
- 5Division of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang Medical Center, Hanyang University College of Medicine, Seoul, Korea .
Abstract
Background: Matrix metalloproteinases (MMPs) play a key role in cavity formation in tuberculosis (TB) and are associated with disease progression and transmission. However, the genetic determinants of inter-individual variability, which influence the expression and signaling of MMP-related genes, remain poorly understood.
Methods: Small-scale whole-genome sequencing targeting MMPs was conducted on peripheral blood samples from 20 adult patients with TB to investigate genetic determinants of cavity formation. Following variant calling, statistical association analyses were performed using the Exact Association Test and Fisher’s exact test as well as pathway and network analyses, with appropriate corrections for multiple testing.
Results: Eleven TB patients with cavitation and nine without cavitation were analyzed. Thirty genes related to extracellular matrix remodeling and MMP activity were identified as significantly associated with cavity formation using the Exact Association Test. Fisher’s exact test revealed 35 single-nucleotide polymorphisms in patients with cavitary TB, including variants regulating key genes such as KLKB1, LAMB3, LTBP4, ITGB2, and EGFR. Network analysis demonstrated that the implicated genes were broadly distributed across the genome and linked to distinct biological pathways involved in TB cavitation.
Conclusion: This study identifies host genetic variants associated with TB cavity formation, particularly those involved in MMP activity, extracellular matrix remodeling, and immune signaling, supporting a multifactorial model of tissue destruction. These findings offer preliminary insights into host genetic contributors to cavitary TB.
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BibTeX
@article{zo2026investigation,
title = {{Investigation of Matrix Metalloproteinase–Related Genetic Variations Associated With Cavity Formation in Pulmonary Tuberculosis}},
author = {Sungmin Zo and Hayoung Choi and Sang Hyuk Kim and Ye Eun Yoon and Jae Won Yun and Hyun Lee},
journal = {Journal of Korean Medical Science},
year = {2026},
month = jun,
doi = {10.3346/jkms.2026.41.e262},
url = {https://doi.org/10.3346/jkms.2026.41.e262},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Investigation of Matrix Metalloproteinase–Related Genetic Variations Associated With Cavity Formation in Pulmonary Tuberculosis
AU - Sungmin Zo
AU - Hayoung Choi
AU - Sang Hyuk Kim
AU - Ye Eun Yoon
AU - Jae Won Yun
AU - Hyun Lee
PY - 2026
DA - 2026/06/29
JO - Journal of Korean Medical Science
DO - 10.3346/jkms.2026.41.e262
UR - https://doi.org/10.3346/jkms.2026.41.e262
AB - Background: Matrix metalloproteinases (MMPs) play a key role in cavity formation in tuberculosis (TB) and are associated with disease progression and transmission. However, the genetic determinants of inter-individual variability, which influence the expression and signaling of MMP-related genes, remain poorly understood. Methods: Small-scale whole-genome sequencing targeting MMPs was conducted on peripheral blood samples from 20 adult patients with TB to investigate genetic determinants of cavity formation. Following variant calling, statistical association analyses were performed using the Exact Association Test and Fisher’s exact test as well as pathway and network analyses, with appropriate corrections for multiple testing. Results: Eleven TB patients with cavitation and nine without cavitation were analyzed. Thirty genes related to extracellular matrix remodeling and MMP activity were identified as significantly associated with cavity formation using the Exact Association Test. Fisher’s exact test revealed 35 single-nucleotide polymorphisms in patients with cavitary TB, including variants regulating key genes such as KLKB1, LAMB3, LTBP4, ITGB2, and EGFR. Network analysis demonstrated that the implicated genes were broadly distributed across the genome and linked to distinct biological pathways involved in TB cavitation. Conclusion: This study identifies host genetic variants associated with TB cavity formation, particularly those involved in MMP activity, extracellular matrix remodeling, and immune signaling, supporting a multifactorial model of tissue destruction. These findings offer preliminary insights into host genetic contributors to cavitary TB.
SN - 1011-8934
SN - 1598-6357
ER -