doi:10.1038/nindia.2008.217 Published online 9 June 2008
Interferon-gamma (IFNγ), a Th1 cytokine or regulatory protein, plays a protective role in asthma. The region encompassing IFNγ gene is linked with asthma. Researchers now pinpoint1 that polymorphism in the non-coding region of the gene is associated with asthma.
Childhood asthmatics who later resolve their asthma symptoms have higher levels of IFNγ compared to those who don't, thus providing a clue that individual variations in the regulatory regions of the gene could play significant role in the origin and development of asthma.
"As polymorphisms in the coding region of IFNγ gene were found not to be associated with asthma in earlier studies, we investigated polymorphisms in the non-coding region," says lead researcher Balram Ghosh from the Molecular Immunogenetics Laboratory at the Institute of Genomics and Integrative Biology in New Delhi. This is the first comprehensive study where polymorphisms spanning the whole IFNγ gene have been investigated.
The team used population based studies (case-control and family cohorts independently), to demonstrate that polymorphisms in the non-coding region, especially A/G polymorphism in intron 3 of IFNγ, is associated with asthma. The polymorphic allele (G) was found with higher frequency in normal controls than asthmatics.
"Furthermore, our data suggest that the region encompassing intron 1 and intron 3 is very significant in an individual's predisposition to asthma," he says.
The team also demonstrated that the A/G polymorphism changes affinity for certain nuclear factors and thus could be involved in altering the levels of IFNγ expression which, in turn, may lead to asthma susceptibility. Identifying disease specific regulatory regions in IFNγ could be useful in designing appropriate therapeutic interventions for asthma and other immunological disorders where IFN-a plays a key role, he adds.