MUTATION SCREENING OF INTERFERON-GAMMA (IFN-GAMMA) AS A CANDIDATE GENE FOR ASTHMA

Background Reduced levels of interferon gamma (IFN gamma) mRNA and pro tein 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 c hromosome 12; a region of the genome which has been shown in linkage s tudies to be associated with asthma. Objective To determine if there a re any mutations present in the coding exons and 5' flanking region of the IFN gamma gene in atopic asthmatic subjects compared with control s to explain the lower levels of this cytokine as an inherited, rather than acquired, factor in the asthmatic subjects. Methods The four exo ns and 5' flanking region of the IFN gamma gene were amplified by poly merase 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 heteroduple x analyses to see if there were any changes in the DNA migration patte rns which would suggest the presence of a sequence variation. Results The four exons and the 5' flanking region of the IFN gamma gene were a mplified from 265 individuals from two populations. Single strand conf ormational polymorphism and heteroduplex analyses did not reveal any m utations in the regions examined. Conclusion The gene for IFN gamma ap pears to be highly conserved as no sequence variations were detected i n 265 individuals. These results suggest that mutations of the IFN gam ma gene are unlikely to be a significant cause of an inherited asthma diathesis.