title: Variants in the IFNγ transcription factor genes TBET, STAT1, STAT4, and HLX and the risk of pulmonary tuberculosis in a Colombian population: a case-control study.
abstract: BACKGROUND
  Interferon gamma (IFNγ) is the most potent cytokine involved in the control of Mycobacterium tuberculosis (Mtb), the etiological agent of human tuberculosis (TB). Patients with active TB present reduced levels of IFNγ, which may explain the lack of effective immunity against Mtb in these patients. The diminished expression of or functional alterations in trans-acting factors that regulate IFNγ gene expression may explain the reduced levels of IFNγ in TB patients.
  
  
  OBJECTIVE
  To investigate the relationships of genetic variants in the transcription factors TBET, STAT1, STAT4, and HLX to susceptibility/resistance to pulmonary TB.
  
  
  METHODS
  Eight candidate single-nucleotide polymorphisms (SNPs) were selected, and genotyped in 466 unrelated pulmonary TB patients and 300 healthy controls from Colombia, and the allelic and genetic associations with TB were analyzed.
  
  
  RESULTS
  The results indicate that no SNP in the transcription factors studied is associated with TB. However, polymorphism rs11650354 in the TBET gene may be associated with a decreased risk of TB; the TT genotype was significantly associated with TB protection in a recessive genetic model (OR=0.089, 95% CI: 0.01-0.73, p=0.0069), although this association was not maintained after multiple test correction (EMP2= 0.61).
  
  
  CONCLUSIONS
  In this study, the rs11650354 variant of TBET was suggested to promote resistance to TB in a Colombian population. A future replication case-control study using additional samples will be necessary to confirm this suggestive association.
authors.affiliation: Stanley S. Scott Cancer Center, Health Science Center, Louisiana State University.
authors.forename: Dulfary
authors.initials: D
authors.lastname: Sánchez
authors.affiliation: ECOGENE-21 Clinical Trial Center, Stanley S. Scott Cancer Center, Centre de Médecine Génique Communautaire de l´Université de Montréal Centre Hospitalier Affilié, Pavillon Notre-Dame.
authors.forename: Céline
authors.initials: C
authors.lastname: Lefebvre
authors.affiliation: Centro Colombiano de Investigación en Tuberculosis (CCITB), Medellín, Colombia.
authors.forename: Luis F
authors.initials: LF
authors.lastname: García
authors.affiliation: Grupo de Inmunología Celular e Inmunogenética (GICIG), Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Barrera
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003105:Colombia; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D050794:STAT1 Transcription Factor / Q000235:genetics; D050797:STAT4 Transcription Factor / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014397:Tuberculosis, Pulmonary / Q000235:genetics*; D000098815:T-bet Transcription Factor
chemical_list: C084058:HLX protein, human; D018398:Homeodomain Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D007371:Interferon-gamma