ScienceDaily (Sep. 21, 2005) — New Haven, Conn.-Yale School of Medicine researchers identified a gene prevalent in the population that controls the clinical severity of asthma, according to their report in this week's Proceedings of the National Academy of Sciences.

Richard Bucala, M.D., professor in the Department of Internal Medicine and senior author of the study, said that once you have asthma, there are genes that are going to control how bad it is.

"Asthma patients who have high production variants of the macrophage migration inhibitory factor gene (MIF) are more likely to have severe disease," he said.

Asthma is a clinical syndrome of airway inflammation, excessive response, and airflow obstruction to the lungs. Patients with asthma produce MIF, a gene product that regulates immunity, in their serum and in the fluid that lines their lungs.

The study by Bucala and his colleagues in Dublin, Ireland, included experiments in mice that are resistant to developing asthma because they lack the gene, and an examination of a human population in Dublin chosen for their similar ethnic and geographic identity.

When challenged with a trigger for their asthma attack, the genetically deficient mice had less pulmonary inflammation and lower airway hyper-responsiveness than genetically matched, wild-type control mice. Similarly, in an analysis of 151 Caucasian patients with mild, moderate and severe asthma, there was a significant association between mild asthma and the low expression of MIF.

"These results support an important role for MIF in the pathogenesis of human asthma," Bucala said. "A drug treatment to lower MIF in patients may be beneficial and could be guided by the MIF genotype of affected individuals."

PNAS 102: 14410-14415 (online week of Sept. 19 and in print on Oct. 4, 2005)

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