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PLoS One. 2014 Jul 9;9(7):e99496. doi: 10.1371/journal.pone.0099496. eCollection 2014.

Polymorphisms of SP110 are associated with both pulmonary and extra-pulmonary tuberculosis among the Vietnamese.

Author information

1
Respiratory and Environmental Epidemiology Research Group, Woolcock Institute of Medical Research, Glebe, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia; Tuberculosis Research Group, Centenary Institute, Newtown, Sydney, Australia.
2
National Lung Hospital, Ba Dinh, Hanoi, Vietnam.
3
Sydney Medical School, University of Sydney, Sydney, Australia; Department of Medical Genomics, Royal Prince Alfred Hospital, Camperdown, Sydney, Australia.
4
Tuberculosis Research Group, Centenary Institute, Newtown, Sydney, Australia.
5
Hanoi Medical University, Hanoi, Vietnam.
6
Hanoi Lung Hospital, Hanoi, Vietnam.
7
Respiratory and Environmental Epidemiology Research Group, Woolcock Institute of Medical Research, Glebe, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia; Liverpool Hospital, Liverpool, Sydney, Australia.
8
Sydney Medical School, University of Sydney, Sydney, Australia; Tuberculosis Research Group, Centenary Institute, Newtown, Sydney, Australia.

Abstract

BACKGROUND:

Tuberculosis (TB) is an infectious disease that remains a major cause of morbidity and mortality worldwide, yet the reasons why only 10% of people infected with Mycobacterium tuberculosis go on to develop clinical disease are poorly understood. Genetically determined variation in the host immune response is one factor influencing the response to M. tuberculosis. SP110 is an interferon-responsive nuclear body protein with critical roles in cell cycling, apoptosis and immunity to infection. However association studies of the gene with clinical TB in different populations have produced conflicting results.

METHODS:

To examine the importance of the SP110 gene in immunity to TB in the Vietnamese we conducted a case-control genetic association study of 24 SP110 variants, in 663 patients with microbiologically proven TB and 566 unaffected control subjects from three tertiary hospitals in northern Vietnam.

RESULTS:

Five SNPs within SP110 were associated with all forms of TB, including four SNPs at the C terminus (rs10208770, rs10498244, rs16826860, rs11678451) under a dominant model and one SNP under a recessive model, rs7601176. Two of these SNPs were associated with pulmonary TB (rs10208770 and rs16826860) and one with extra-pulmonary TB (rs10498244).

CONCLUSION:

SP110 variants were associated with increased susceptibility to both pulmonary and extra-pulmonary TB in the Vietnamese. Genetic variants in SP110 may influence macrophage signaling responses and apoptosis during M. tuberculosis infection, however further research is required to establish the mechanism by which SP110 influences immunity to tuberculosis infection.

PMID:
25006821
PMCID:
PMC4090157
DOI:
10.1371/journal.pone.0099496
[Indexed for MEDLINE]
Free PMC Article

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