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Published on: October 28, 2019
Polymorphisms in autophagy genes and susceptibility to tuberculosis
Mario Songane1, Johanneke Kleinnijenhuis, Bachti Alisjahbana
1Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Plos One
|August 11, 2012
Summary
This study investigated autophagy gene variations and their link to tuberculosis (TB) susceptibility and M. tuberculosis Beijing genotype infection. No clear associations were found between autophagy gene polymorphisms and TB or cytokine production.
Area of Science:
- Genetics
- Immunology
- Microbiology
Background:
- Autophagy plays a role in controlling intracellular Mycobacterium tuberculosis infections.
- Previous studies linked autophagy gene IRGM polymorphisms to tuberculosis (TB) susceptibility and specific M. tuberculosis genotypes.
Purpose of the Study:
- To investigate the association between polymorphisms in 14 autophagy genes and TB in an Indonesian population.
- To examine correlations between autophagy gene polymorphisms, M. tuberculosis genotypes, and ex-vivo cytokine production.
Main Methods:
- Genotyping of 22 polymorphisms across 14 autophagy genes in 1022 Indonesian TB patients and 952 controls.
- Spoligotyping to determine M. tuberculosis genotypes in infected patients.
- Correlation analysis with ex-vivo production of TNF, IL-1β, IL-6, IL-8, IFN-γ, and IL-17 in healthy volunteers.
Main Results:
- No significant association was found between TB and polymorphisms in most autophagy genes studied (ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1, LAMP3, P2RX7, WIPI1, MTOR, ATG4C).
- A weak association was observed between LAMP1 and MTOR polymorphisms and infection with the M. tuberculosis Beijing genotype (p = 0.02), which lost significance after multiple testing correction.
- A single polymorphism in ATG10 showed a link with IL-8 production (p = 0.04), also not significant after correction.
Conclusions:
- This comprehensive analysis of autophagy gene polymorphisms does not establish a clear link with tuberculosis susceptibility in the Indonesian population.
- No significant association was found between the studied autophagy gene polymorphisms and infection with the M. tuberculosis Beijing genotype.
- The examined autophagy gene polymorphisms were not significantly associated with ex-vivo pro-inflammatory cytokine production in response to M. tuberculosis.
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