Mutation in the gene responsible for cystic fibrosis and predisposition to chronic rhinosinusitis in the general population.
BACKGROUND
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.


METHODS
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.


METHODS
Otolaryngology-head and neck clinic of a US teaching hospital.


METHODS
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.


METHODS
Presence of CF mutations by DNA analysis among CRS patients vs controls.


RESULTS
Eleven CRS patients were found to have a CF mutation (DeltaF508, 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 DeltaF508 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).


CONCLUSIONS
These data indicate that mutations in the gene responsible for CF may be associated with the development of CRS in the general population. JAMA. 2000;284:1814-1819.
Wang
X
X
McKusick-Nathans Institute of Genetic Medicine, CMSC 1004, Baltimore, MD 21287, USA.
Moylan
B
B
Leopold
D A
DA
Kim
J
J
Rubenstein
R C
RC
Togias
A
A
Proud
D
D
Zeitlin
P L
PL
Cutting
G R
GR
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D012220:Rhinitis / Q000175:diagnosis / Q000235:genetics*; D012852:Sinusitis / Q000175:diagnosis / Q000235:genetics*; D013542:Sweat / Q000737:chemistry
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator