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Polymorphisms of SP110 Are Associated with both Pulmonary and Extra-Pulmonary Tuberculosis among the Vietnamese

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Listed:
  • Gregory J Fox
  • Dinh Ngoc Sy
  • Nguyen Viet Nhung
  • Bing Yu
  • Magda K Ellis
  • Nguyen Van Hung
  • Nguyen Kim Cuong
  • Luu Thi Lien
  • Guy B Marks
  • Bernadette M Saunders
  • Warwick J Britton

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.

Suggested Citation

  • Gregory J Fox & Dinh Ngoc Sy & Nguyen Viet Nhung & Bing Yu & Magda K Ellis & Nguyen Van Hung & Nguyen Kim Cuong & Luu Thi Lien & Guy B Marks & Bernadette M Saunders & Warwick J Britton, 2014. "Polymorphisms of SP110 Are Associated with both Pulmonary and Extra-Pulmonary Tuberculosis among the Vietnamese," PLOS ONE, Public Library of Science, vol. 9(7), pages 1-9, July.
    • Handle: RePEc:plo:pone00:0099496
    DOI: 10.1371/journal.pone.0099496
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    1. Hui Pan & Bo-Shiun Yan & Mauricio Rojas & Yuriy V. Shebzukhov & Hongwei Zhou & Lester Kobzik & Darren E. Higgins & Mark J. Daly & Barry R. Bloom & Igor Kramnik, 2005. "Ipr1 gene mediates innate immunity to tuberculosis," Nature, Nature, vol. 434(7034), pages 767-772, April.
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