Potential role for the common cystic fibrosis DeltaF508 mutation in Crohn's disease.
BACKGROUND
Inflammatory bowel disease (IBD) is an epithelial barrier disease that is thought to result from a dysregulated interaction with bacteria in the intestine of genetically predisposed individuals. The cystic fibrosis transmembrane conductance regulator (CFTR), which is mutated in the autosomal recessive disease cystic fibrosis, modulates gut permeability, mucus production, and epithelial interactions with bacteria. The cystic fibrosis DeltaF508 mutation is commonly found in the general population and has been shown to result in a reduced number of CFTR molecules at the surface of epithelial cells. Given the important biological functions of CFTR in the intestine, we tested whether this mutation is of relevance to IBD.


METHODS
Using DNA heteroduplex analysis, we investigated the distribution of DeltaF508 heterozygosity in 2568 subjects from three independent cohorts of Italian, Swedish, and Scottish IBD patients and controls.


RESULTS
In all three cohorts an association between DeltaF508 and Crohn's disease (CD) was observed. Specifically, DeltaF508 heterozygosity was markedly underrepresented in CD patients from Italy and Sweden (P = 0.021 and 0.027 versus controls, respectively), while stratification for disease location revealed an absence of DeltaF508 carriers among Scottish CD patients with right-sided colitis (P = 0.023 versus all other locations).


CONCLUSIONS
DeltaF508 heterozygosity might exert a protective effect in CD.
Bresso
Francesca
F
Strategic Research Center IRIS, Karolinska Institutet, Stockholm, Sweden.
Askling
Johan
J
Astegiano
Marco
M
Demarchi
Brunello
B
Sapone
Nicoletta
N
Rizzetto
Mario
M
Gionchetti
Paolo
P
Lammers
Karen M
KM
de Leone
Annalisa
A
Riegler
Gabriele
G
Nimmo
Elaine R
ER
Drummond
Hazel
H
Noble
Colin
C
Torkvist
Leif
L
Ekbom
Anders
A
Zucchelli
Marco
M
Lofberg
Robert
R
Satsangi
Jack
J
Pettersson
Sven
S
D'Amato
Mauro
M
D000293:Adolescent; D000328:Adult; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000502:physiology; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012606:Scotland; D013548:Sweden
D019005:Cystic Fibrosis Transmembrane Conductance Regulator