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

• Published in: PloS one Vol. 9; no. 7; p. e99496
• Main Authors: Fox, Gregory J., Sy, Dinh Ngoc, Nhung, Nguyen Viet, Yu, Bing, Ellis, Magda K., Van Hung, Nguyen, Cuong, Nguyen Kim, Thi Lien, Luu, Marks, Guy B., Saunders, Bernadette M., Britton, Warwick J.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.07.2014; Public Library of Science (PLoS)
• Subjects: Adult; Analysis; Apoptosis; Asian Continental Ancestry Group - genetics; Biological response modifiers; Biology and Life Sciences; Case-Control Studies; Epidemiology; Ethics; Female; Genetic aspects; Genetic Association Studies - methods; Genetic diversity; Genetic variance; Health aspects; Hospitals; Humans; Immune response; Immune system; Immunity; Infections; Infectious diseases; Interferon; Lung diseases; Macrophages; Macrophages - metabolism; Male; Medical research; Medical schools; Medicine and Health Sciences; Middle Aged; Minor Histocompatibility Antigens; Morbidity; Mortality; Nuclear Proteins - genetics; Polymorphism; Polymorphism, Single Nucleotide; Population; Proteins; Public health; Risk factors; Signaling; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Systematic review; Tuberculosis; Tuberculosis - genetics; Tuberculosis - immunology; Tuberculosis - pathology; Vietnam; Young Adult; Sydney New South Wales Australia; Australia; Vietnam
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0099496

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. 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. 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). 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.