Gene That Controls The Severity Of Asthma Identified

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

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

Asthma is a clinical syndrome of airway inflammation,excessive response, and airflow obstruction to the lungs. Patients withasthma produce MIF, a gene product that regulates immunity, in theirserum 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 asthmabecause they lack the gene, and an examination of a human population inDublin chosen for their similar ethnic and geographic identity.

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

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

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