Comprehensive Analysis of Pathogenic Variants in Tuberculosis Susceptibility Genes and Their Correlation with Incidence Rates Across Multiple Continents: A Comparative Study

Pathogenic variants in TB susceptibility genes

  • Danang P. Amukti Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, Indonesia
  • Lalu M Irham Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, Indonesia
  • Wirawan Adikusuma Departement of Pharmacy, University of Muhammadiyah Mataram, Mataram, Indonesia; Research Center for Computing, Research Organization for Electronics and Informatics, National Research and Innovation Agency (BRIN), Cibinong Science Center, Cibinong 16911, Indonesia
  • Sabiah Khairi School of Nursing, College of Nursing, Taipei Medical University, Taipei 11031, Taiwan
  • Petrina T Philothra Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
  • Ichtiarini N Santri Faculty of Public Health, Universitas Ahmad Dahlan, Yogyakarta 55164, Indonesia
  • Isom Hilmi Departement of Physics, Faculty of Applied Science and Technology, Universitas Ahmad Dahlan, Yogyakarta, Indonesia
  • Rockie Chong Department of Chemistry and Biochemistry, University of California, Los Angeles, USA.
DOI: https://doi.org/10.46829/hsijournal.2026.4.8.2.1476-1489
Keywords: bioinformatics, tuberculosis, genomic variants, susceptibility genes, drug discovery, drug repurposing, therapeutic targets

Abstract

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains one of the leading infectious diseases worldwide. Host genetic variation plays a crucial role in determining susceptibility to TB infection; however, the distribution and impact of genetic variants across global populations are not yet fully understood.
Objective: This study aimed to identify genetic variants associated with susceptibility to TB infection and to evaluate their allele frequencydistribution and correlation with TB incidence across different populations..
Methods: A bioinformatics approach was employed to analyze four key genetic variants: rs35296992 (LGSN), rs9272785 (HLA-DQA1), rs41553512 (HLA-DRB5), and rs2269497 (RGS12). Analyses included global allele frequency distribution, correlation testing with TB incidence, and gene expression profiling across multiple tissues.
Results: The findings revealed significant geographic variation in allele frequencies. American populations exhibited higher frequencies of rs41553512 and rs2269497, African populations showed the highest frequency of rs9272785, while European populations had the highest frequency of rs35296992. Correlation analysis demonstrated a positive association between all variants and TB incidence, with rs9272785
showing the strongest correlation, followed by rs35296992. Variants rs41553512 and rs2269497 also showed significant but weaker correlations. Additionally, these variants exhibited distinct expression patterns in lung, liver, and whole blood tissues, highlighting their potential role in immune response mechanisms.
Conclusion: The identified genetic variants significantly contribute to TB susceptibility and display population-specific distributions. These findings emphasize the importance of genomic approaches in understanding host–pathogen interactions and support the development of personalized therapeutic strategies. Such insights may enhance TB prevention and treatment outcomes across diverse populations.

Author Biography

Lalu M Irham, Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, Indonesia

Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, Indonesia

Published
2026-03-30
Issue
Vol 8 No 2 (2026): Health Sciences Investigations (HSI)  Journal
Section
Original Research Article