Hopkins Researchers Uncover Sinus Infection-CF Gene Link

Scientists at Johns Hopkins report that some people who suffer with repeated sinus infections may bepredisposed to them in part because they carry the same genetic mutation responsible for cysticfibrosis(CF).

An estimated 30 million Americans have chronic sinus disease, accounting for billions of dollarsspent yearly on lost work days, doctor visits and remedies.

In a study published in the current edition of The Journal of the American Medical Association, theresearchers found that 7 percent of 147 patients who recently visited Hopkins because of repeatedbouts of sinusitis carried a copy of the mutated gene responsible for CF, called CFTR. The scientistspredict that risk of chronic sinusitis will likely double if you're a CF gene carrier.

"We want to be clear that these patients don't have cystic fibrosis," says geneticist Garry R. Cutting,M.D., of the research team. Cystic fibrosis results from a double dose of the mutant CFTR gene--both parents must contribute a copy of this recessive gene for CF to result. "But we've longwondered if having just one mutant CFTR gene has any health effects," says Cutting.

"Now we can confirm what we've suspected. For years we've known that children and adults withCF have severe sinus infections --it's almost a given with the disease." Cystic fibrosis is marked byabnormal salt concentrations and abnormally thick mucus in the respiratory tract and elsewhere. The mucus blocks facial sinuses and, along with the abnormal salt content, provides an environmentthat promotes bacterial growth. "That said, we don't recommend that everyone with chronic sinus problems get their CFTR genestested," Cutting warns. "The research is still at an early stage. The knowledge may prove usefultherapeutically, however. Some sinusitis patients might be helped by treatments developed for CF. Further, genetic testing may allow us to single out patients with the most severe form of chronicsinusitis, those who may benefit from therapy aimed precisely at their underlying problem."

In the current study, the researchers analyzed blood samples from the 147 sinus sufferers, and from alike number of controls, for any of 16 of the most common mutations of the CF gene. They alsoanalyzed differences in the capacity for patients' nasal tissues to carry a current --a good measure ofcells' salt output.

Ten of the sinusitis patients were found to be carriers of a mutated CF gene, most with thecommonest form of mutation. Only two of the control group were carriers.

Both the sinusitis and control patients tested within normal range in the nasal conductance tests,though the sinusitis patients had slight abnormalities, probably due, Cutting says, to the mutant CFgene.

Very little is known about why chronic sinus infections occur, the researchers say. "Knowing whichgenes are involved tells us how to approach underlying biology and may suggest smarter ways todeal with disease," says Cutting. "For example, patients with a sinus infection typically take agentslike Sudafed, which have a drying effect. But in a respiratory infection," he says, "cells lining thesinuses are forced to produce more fluid. In patients carrying a mutant CFTR gene, this mayseverely tax cells where water output is already below par, perhaps increasing susceptibility toinfection. This could mean, for people carrying mutant forms of CFTR, that using such drugs ortaking their sinuses to Arizona might not be the best idea." The researchers will extend their work to see if the sinuses of carrier patients respond differentlyfrom others to stresses such as cold viruses or cold air. "This could point the way to drug trials andpotentially, to new, targeted ways to treat sinus infections," Cutting says.

The research was funded by grants from the National Institutes of Health and the Cystic FibrosisFoundation.

First author on the study is Xin Jing Wang, M.D., Ph.D. Others on the research team are: Donald A.Leopold, M.D., Jean Kim, M.D., Ph.D., Ronald C. Rubenstein, M.D., Ph.D., Alkis Togias, M.D.,and Pamela L. Zeitlin, M.D., Ph.D.

Related Web sites:

For the Cystic Fibrosis Foundation -- http://www.cff.org

For an A-Z on sinus infections -- http://www.sinuses.com/faq.htm

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Media Contact: Marjorie Centofanti 410-955-8725
Email: mcentofanti@jhmi.edu