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
Introduction: 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.
Materials and 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 multipletest correction (EMP2= 0.61).
Conclusion: In this study, the rs11650354 variant of TBET was suggested to promote resistance toTB in a Colombian population. A future replication case-control study using additional samples will be necessary to confirm this suggestive association.
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