Polymorphism in the First Intron of Interferon-Gamma Gene (+874T/A) in Patients with BCG Adenitis

Background: Cytokines and specially interferon-gamma (IFN-gamma) are largely responsible for the regulation of the protective immune response against mycobacterial infections. Several studies have clarified the importance of common variants of IFN-gamma gene regarding the susceptibility to tuberculosis. Bacille Calmette-Guerin (BCG) vaccine that is used to prevent severe forms of tuberculosis could produce local and systemic side effects. In this study we hypothesized that the IFN-gamma (+874T/A) polymorphism was associated with development of BCG adenitis. Methods: Thirty patients with BCG adenitis (18 males and 12 females) and 30 age and sex-matched healthy children, vaccinated with BCG during the first two days of life were chosen. All the patients and controls were of Iranian Fars origin and the study was conducted from 2005 to 2007. DNA samples were obtained from 30 patients with BCG adenitis and 30 age and sex matched healthy vaccinees. Polymorphism at +874 was identified using allele specific polymerase chain reaction. Allele and genotype frequencies in cases and controls were compared using the chi(2) test and odds ratios (OR) and their 95% confidence intervals (CI) were calculated. Results: The minor allele (T) frequency was significantly lower in patients with BCG adenitis compared to controls (35% vs. 55%, P=0.02, OR=0.441, 95% Cl=0.211-0.919). The Armitage trend test revealed a gradually increasing protection from the AA genotype through AT to TT (common odds ratio=0.49; P=0.037). Conclusion: Our data suggest that in an Iranian population, the IFN-gamma(+874T/A) polymorphism is associated with development of BCG adenitis in the vaccinees.