The Johns Hopkins team that first unearthed two chromosomes as the site of genes for asthma and allergic disease has moved closer to identifying those genes with the help of a unique Barbados island population.
"Allergic disease involves multiple genes and is incredibly complicated, making it hard to sort out genetic and environmental factors," says Kathleen Barnes, the principal investigator of the study, which appears in the current issue of Genomics. "Because the Barbados group is environmentally homogenous, is exposed to the same kinds and levels of allergens, eats similar foods, lives in the same types of homes and climate and has similar genetic makeup (an admixture of West Africa and English Caucasians), we had a reduced number of confusing factors to sort through to pinpoint genetic culprits."
Among other things, the Barbados study provides some of the first evidence that particular genes work in concert to produce asthma. The researchers report that one region on chromosome 12q and two on 17q appear to contain collaborating genes that control risk of increased levels of IgE, antibodies produced by the immune system that cause allergic reactions. Although the precise genes on chromosomes 12 and 17 are not known at this time, the markers that the group used to identify linkage are situated very close to candidate genes believed to play important roles in allergic disease by producing factors that promote the development of inflammation. Barnes and her colleagues identified chromosomes 12 and 17 as allergic disease gene sites in 1996 and 2000, respectively.
To get their results, the gene hunters identified and sequenced 29 markers on DNA from 29 Barbados families and aligned these with levels of asthma in 507 individuals, including 154 with asthma. The scientists determined allergic disease by measuring levels of IgE.
"Until now, no study has demonstrated gene-gene interaction in asthma," says Barnes, an assistant professor of clinical immunology. "If we can begin to tease out more of the gene-gene interactions in these pathways, as we did in this study, we can come up with better drugs targeted at specific points in the pathway to prevent symptoms."
While the isolated nature of the study group made the discovery possible, Barnes cautions that, even in light of the similarities among families living in Barbados, much of the interaction observed was driven by a single, large, extended family in the study. "This indicates to us that you must have just the right genetic and environmental conditions to find linkage to asthma genes, and it reminds us just how complex this disease really is," she says.
About one of every five adults and children in the United States has allergies, including allergic asthma. Asthma is a chronic disease in which airflow in and out of the lungs may be blocked by muscle squeezing, swelling and excess mucus. In 1997, more than 30.5 million prescriptions were filled for asthma medication, and patients had approximately 1.2 million emergency room visits and 445,000 hospitalization days.
Other Hopkins researchers who contributed to this study include Rasika Mathias, Vincenzo Casolaro, Terri Beaty, Linda Freidhoff, Renate Nickel, Maria Stockton and Xielun Xue. Funding for the research was provided by the Allergy and Asthma Foundation of America and the National Institutes of Health.
For more information about asthma and allergy research at Johns Hopkins, go to http://www.hopkins-allergy.org.