Gene Alterations for Cystic Fibrosis May Also Account for Chronic Sinus Problems in Some
Gene alterations known to cause the inherited disorder cystic fibrosis (CF), which is characterized by mucous membrane abnormalities in the lungs, appear also to contribute to chronic sinus problems in some people, according to a report in this week's Journal of the American Medical Association. About 14 percent of the general U.S. population suffers from chronic sinusitis, a persistent and often painful inflammation of the mucous membranes in the sinus cavities around the nose and eyes and forehead. The disease occurs frequently in patients with asthma and also in people with allergic rhinitis.
"The study is among the first to investigate the genetic basis of chronic sinusitis, a common and troublesome disorder. It provides new insights into the cause of the disease in some people and points to new strategies for diagnosis and treatment," says Marshall Plaut, M.D., of the National Institute of Allergy and Infectious Diseases (NIAID). "It represents a new and important research direction."
The study was supported by NIAID, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Center for Research Resources, all components of the National Institutes of Health (NIH). The Cystic Fibrosis Foundation also supported the research.
Because chronic sinusitis occurs commonly in people with CF, a disorder now diagnosed by the presence of alterations in a gene known as CFTR, Garry Cutting, M.D., and his colleagues at the Johns Hopkins University in Baltimore, wanted to know if changes in the CFTR gene might also play a role in sinusitis in people who don't have CF. So they compared the DNA of 147 patients with sinusitis, who came to their ear-nose-and-throat clinic, to that of 123 people without sinusitis. Patients with cystic fibrosis were excluded from the study.
CFTR's usual job is to regulate the flow of salt and water across the cell membrane. People with cystic fibrosis carry two copies of an altered CFTR gene, which affects the membranes in the lungs and leads to accumulation of thick, sticky mucous that is not only difficult to clear, but also provides a breeding ground for bacteria.
Dr. Cutting wondered whether at least some people with chronic sinusitis in the general population carry a single copy of a CFTR alteration that causes CF and whether that alteration contributes to their sinusitis. The results confirmed this hypothesis. In addition, almost all the patients with chronic sinusitis and a CF-associated CFTR alteration expressed a second CFTR gene variant called M470V, which is not associated with CF and occurs in 50 percent of the general population.
The frequency of CFTR gene alterations associated with CF in the general population is about 3.6 percent. Analysis of the DNA samples from the patient volunteers revealed CF mutations in the CFTR gene in 10 of the 147 volunteers who had chronic sinusitis but not CF. Each of the sinusitis sufferers had characteristic thickening of the mucous membranes in their noses or sinuses. The results showed the sinusitis sufferers were nearly five times more likely than their healthy counterparts to carry a CFTR alteration associated with CF. Of the 10 patients who did have CF-linked alterations, 9 also carried another CFTR variant known as M470V, which occurs in about 50 percent of the general population.
In recent years, chronic sinusitis has accounted for over 11 million visits to doctor's offices. Often, the condition can be controlled with decongestants, antihistamines, and nasal corticosteroid sprays and sometimes antibiotics. Several of the patients in Dr. Cutting's study had also received sinus surgery multiple times. Yet even those efforts fail to relieve the condition in some patients.
Reference: XJ Wang et al. Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population. JAMA 284(14):1814-19 (2000).
NIAID is a component of the National Institutes of Health(NIH). NIAID supports basic and applied research to prevent, diagnose and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
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