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Published on: April 1, 2019
A polymorphism in the P2X7 gene increases susceptibility to extrapulmonary tuberculosis
Suran L Fernando1, Bernadette M Saunders, Ronald Sluyter
1Mycobacterial Research Programme, Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag No 6, Newtown, NSW, Australia.
American Journal of Respiratory and Critical Care Medicine
|November 11, 2006
Summary
Genetic variations in the P2X7 gene increase susceptibility to tuberculosis (TB). A specific P2X7 polymorphism (1513C allele) impairs macrophage function, raising the risk of extrapulmonary TB.
Area of Science:
- Immunogenetics
- Infectious Diseases
- Molecular Biology
Background:
- Genetic variations influence susceptibility to tuberculosis (TB).
- The P2X7 receptor on macrophages plays a role in controlling mycobacterial infections.
- Specific P2X7 gene polymorphisms have been identified that reduce the ability of macrophages to kill mycobacteria.
Purpose of the Study:
- To investigate the association between P2X7 gene polymorphisms and the risk of developing TB.
- To assess the functional impact of identified P2X7 polymorphisms on macrophage activity against Mycobacterium tuberculosis.
Main Methods:
- Genotyping of P2X7 polymorphisms in individuals from Southeast Asia using case-control cohorts.
- Assessing the functional capacity of P2X7 by measuring ATP-mediated mycobacterial killing and apoptosis in macrophages.
Main Results:
- The 1513A-C polymorphism was prevalent in Southeast Asians, with the 1513C allele linked to reduced Mycobacterium tuberculosis killing.
- The 1513C allele showed a strong association with extrapulmonary TB in two independent cohorts.
- Macrophage-mediated killing of mycobacteria was significantly impaired in individuals with the 1513C allele, correlating with reduced ATP-induced apoptosis.
Conclusions:
- The 1513C allele of the P2X7 gene is a risk factor for extrapulmonary TB.
- This genetic defect leads to impaired macrophage function in killing Mycobacterium tuberculosis, increasing TB susceptibility.
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