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Preliminary Communication
October 11, 2000

Mutation in the Gene Responsible for Cystic Fibrosis and Predisposition to Chronic Rhinosinusitis in the General Population

Author Affiliations

Author Affiliations: McKusick-Nathans Institute of Genetic Medicine (Drs Wang and Cutting), Department of Medicine (Drs Togias and Proud and Ms Moylan), Department of Otolaryngology–Head and Neck Surgery (Drs Leopold and Kim), and Department of Pediatrics (Drs Rubenstein, Zeitlin, and Cutting), Johns Hopkins University School of Medicine, Baltimore, Md. Dr Rubenstein is now affiliated with the Department of Pulmonary Medicine, Children's Hospital of Philadelphia, Philadelphia, Pa.

JAMA. 2000;284(14):1814-1819. doi:10.1001/jama.284.14.1814

Context Chronic rhinosinusitis (CRS) is a common condition in the US general population, yet little is known about its underlying molecular cause. Chronic rhinosinusitis is a consistent feature of the autosomal recessive disorder cystic fibrosis (CF).

Objective To determine whether mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, which is responsible for CF, predispose to CRS.

Design Case-control study conducted from 1996 to 1999 in which the DNA of CRS patients and controls was typed for 16 mutations that account for 85% of CF alleles in the general population. Chronic rhinosinusitis patients with 1 CF mutation were evaluated for a CF diagnosis by sweat chloride testing, nasal potential difference measurement, and DNA analysis for additional mutations.

Setting Otolaryngology–head and neck clinic of a US teaching hospital.

Participants One hundred forty-seven consecutive adult white patients who met stringent diagnostic criteria for CRS and 123 CRS-free white control volunteers of similar age range, geographic region, and socioeconomic status.

Main Outcome Measures Presence of CF mutations by DNA analysis among CRS patients vs controls.

Results Eleven CRS patients were found to have a CF mutation (ΔF508, n = 9; G542X, n = 1; and N1303K, n = 1). Diagnostic testing excluded CF in 10 of these patients and led to CF diagnosis in 1. Excluding this patient from the analyses, the proportion of CRS patients who were found to have a CF mutation (7%) was significantly higher than in the control group (n = 2 [2%]; P = .04, both having ΔF508 mutations). Furthermore, 9 of the 10 CF carriers had the polymorphism M470V, and M470V homozygotes were overrepresented in the remaining 136 CRS patients (P = .03).

Conclusion These data indicate that mutations in the gene responsible for CF may be associated with the development of CRS in the general population.