Mutation screening of interferon-gamma (IFNγ) as a candidate gene for asthma

Background Reduced levels of interferon gamma (IFN gamma) mRNA and protein have been detected in the bronchoalveolar lavage fluid of atopic asthmatics. IFN gamma is secreted by TH1 cells while IL-4 and IL-5 are secreted by TH2 cells and an imbalance in the TH1/TH2 response may be responsible for atopic asthma. The gene for IFN gamma is located on chromosome 12; a region of the genome which has been shown in linkage studies to be associated with asthma. Objective To determine if there are any mutations present in the coding exons and 5' flanking region of the IFN gamma gene in atopic asthmatic subjects compared with controls to explain the lower levels of this cytokine as an inherited, rather than acquired, factor in the asthmatic subjects. Methods The four exons and 5' flanking region of the IFN gamma gene were amplified by polymerase chain reaction (PCR) from genomic DNA of 265 individuals from a Western Australian and a Venezuelan population. The PCR products were examined by single strand conformational polymorphism and heteroduplex analyses to see if there were any changes in the DNA migration patterns which would suggest the presence of a sequence variation. Results The four exons and the 5' flanking region of the IFN gamma gene were amplified from 265 individuals from two populations. Single strand conformational polymorphism and heteroduplex analyses did not reveal any mutations in the regions examined. Conclusion The gene for IFN gamma appears to be highly conserved as no sequence variations were detected in 265 individuals. These results suggest that mutations of the IFN gamma gene are unlikely to be a significant cause of an inherited asthma diathesis.