Gene Alterations for Cystic Fibrosis May Also Account for Chronic SinusProblems in Some

Gene alterations known to cause the inherited disorder cystic fibrosis (CF),which is characterized by mucous membrane abnormalities in the lungs, appearalso to contribute to chronic sinus problems in some people, according to areport in this week's Journal of the American Medical Association. About 14percent of the general U.S. population suffers from chronic sinusitis, apersistent and often painful inflammation of the mucous membranes in thesinus cavities around the nose and eyes and forehead. The disease occursfrequently in patients with asthma and also in people with allergicrhinitis.

"The study is among the first to investigate the genetic basis of chronicsinusitis, a common and troublesome disorder. It provides new insights intothe cause of the disease in some people and points to new strategies fordiagnosis and treatment," says Marshall Plaut, M.D., of the NationalInstitute of Allergy and Infectious Diseases (NIAID). "It represents a newand important research direction."

The study was supported by NIAID, the National Institute of Diabetes andDigestive and Kidney Diseases, and the National Center for ResearchResources, all components of the National Institutes of Health (NIH). TheCystic Fibrosis Foundation also supported the research.

Because chronic sinusitis occurs commonly in people with CF, a disorder nowdiagnosed by the presence of alterations in a gene known as CFTR, GarryCutting, M.D., and his colleagues at the Johns Hopkins University inBaltimore, wanted to know if changes in the CFTR gene might also play a rolein sinusitis in people who don't have CF. So they compared the DNA of 147patients with sinusitis, who came to their ear-nose-and-throat clinic, tothat of 123 people without sinusitis. Patients with cystic fibrosis wereexcluded from the study.

CFTR's usual job is to regulate the flow of salt and water across the cellmembrane. People with cystic fibrosis carry two copies of an altered CFTRgene, which affects the membranes in the lungs and leads to accumulation ofthick, sticky mucous that is not only difficult to clear, but also providesa breeding ground for bacteria.

"Certainly many things contribute to chronic sinusitis in people who have noknown family history of cystic fibrosis," says Dr. Cutting. "But wewondered if at least some sinusitis sufferers in the general populationmight also carry a variant of one copy of the CFTR gene that contributes totheir sinusitis but spares them of cystic fibrosis."

CFTR gene alterations associated with CF occur in about 3.6 percent in thegeneral population. Analysis of the DNA samples from the patient volunteersrevealed CF mutations in the CFTR gene in 10 of the 147 volunteers who hadchronic sinusitis but not CF. Each of the sinusitis sufferers hadcharacteristic thickening of the mucous membranes in their noses or sinuses.The results showed the sinusitis sufferers were nearly five times morelikely than their healthy counterparts to carry a CFTR alteration associatedwith CF. Of the 10 patients who did have CF-linked alterations, 9 alsocarried another CFTR variant known as M470V, which occurs in about 50percent of the general population.

In recent years, chronic sinusitis has accounted for over 11 million visitsto doctors' offices. Often, the condition can be controlled withdecongestants, antihistamines, and nasal corticosteroid sprays and sometimesantibiotics. Several of the patients in Dr. Cutting's study had alsoreceived sinus surgery multiple times. Yet even those efforts fail torelieve the condition in some patients.

NIAID is a component of the NIH. NIAID supports basic and applied researchto prevent, diagnose and treat infectious and immune-mediated illnesses,including HIV/AIDS and other sexually transmitted diseases, tuberculosis,malaria, autoimmune disorders, asthma and allergies.

Press releases, fact sheets and other NIAID-related materials are availableon the NIAID Web site at http://www.niaid.nih.gov.

The National Institute of Allergy and Infectious Diseasesis a component of the National Institutes of Health,U.S. Department of Health and Human Services.Reference:XJ Wang et al. Mutation in the gene responsible for cystic fibrosis andpredisposition to chronic rhinosinusitis in the general population. JAMA284(14):1814-1819 (2000).