title: Polymorphisms of SP110 are associated with both pulmonary and extra-pulmonary tuberculosis among the Vietnamese.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Fox
authors.affiliation: National Lung Hospital, Ba Dinh, Hanoi, Vietnam.
authors.forename: Dinh Ngoc
authors.initials: DN
authors.lastname: Sy
authors.affiliation: National Lung Hospital, Ba Dinh, Hanoi, Vietnam.
authors.forename: Nguyen Viet
authors.initials: NV
authors.lastname: Nhung
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, Australia; Department of Medical Genomics, Royal Prince Alfred Hospital, Camperdown, Sydney, Australia.
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.affiliation: Tuberculosis Research Group, Centenary Institute, Newtown, Sydney, Australia.
authors.forename: Magda K
authors.initials: MK
authors.lastname: Ellis
authors.affiliation: National Lung Hospital, Ba Dinh, Hanoi, Vietnam.
authors.forename: Nguyen
authors.initials: N
authors.lastname: Van Hung
authors.affiliation: Hanoi Medical University, Hanoi, Vietnam.
authors.forename: Nguyen Kim
authors.initials: NK
authors.lastname: Cuong
authors.affiliation: Hanoi Lung Hospital, Hanoi, Vietnam.
authors.forename: Luu
authors.initials: L
authors.lastname: Thi Lien
authors.affiliation: 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.
authors.forename: Guy B
authors.initials: GB
authors.lastname: Marks
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, Australia; Tuberculosis Research Group, Centenary Institute, Newtown, Sydney, Australia.
authors.forename: Bernadette M
authors.initials: BM
authors.lastname: Saunders
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, Australia; Tuberculosis Research Group, Centenary Institute, Newtown, Sydney, Australia.
authors.forename: Warwick J
authors.initials: WJ
authors.lastname: Britton
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014376:Tuberculosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D014744:Vietnam; D055815:Young Adult
chemical_list: D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; C412425:Sp110 protein, human