Polymorphism within the Interferon-gamma/Receptor complex is associated with pulmonary tuberculosis

Rationale: Interferon-γ (IFN-γ) is of central interest in the study of tuberculosis. A number of single-gene mutations have been identified in the IFN-γ signaling pathway that predispose to severe mycobacterial disease, but the relevance of polymorphism within these genes to the common phenotype of tuberculosis remains unclear.Methods: A total of 1,301 individuals were included in a large, detailed study of West African populations with pulmonary tuberculosis. We investigated disease association with the genes encoding IFN-γ and its receptor subunits (IFNG, IFNGR1, and IFNGR2).Results: Within the IFNG gene, two promoter variants showed evidence of novel disease association: −1616GG (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.11–2.00; p = 0.008) and +3234TT (OR, 1.40; 95% CI, 1.09–1.80; p = 0.009). The +874AA genotype was not significantly more frequent among cases over control subjects (OR, 1.16; 95%CI, 0.89–1.51; p = 0.25). In addition, novel disease association was also found with the −56CC ...