The V249I polymorphism of the CX3CR1 gene is associated with fibrostenotic disease behavior in patients with Crohn's disease.
OBJECTIVE
CX3CR1, the receptor of CX3CL1/fractalkine, is involved in regulation of inflammatory response and the CX3CR1-I249-M280 naturally occurring mutants are associated with altered binding to the ligand. Our aim was to evaluate the frequency of CX3CR1 V249I and T280M polymorphisms and NOD2/CARD15 mutations in Crohn's disease patients and to search for a relationship with phenotype.


METHODS
Clinical data were retrospectively collected. V249I and T280M polymorphisms of CX3CR1 gene and NOD2/CARD15 mutations (R702W, G908R, 3020InsC) were identified.


RESULTS
Two hundred and thirty-nine patients (140 females, 39.7+/-14.1 years) were included. About 37.4% were heterozygous and 8.8% were homozygous for the V249I CX3CR1 polymorphism, 18.1% were heterozygous and 1.3% homozygous for the T280M CX3CR1 polymorphism and 35.9% had at least one of the three mutations of NOD2/CARD15. The T280M CX3CR1 polymorphism was not associated with any phenotype. In univariate analysis, stenosis was significantly associated with both V249I CX3CR1 polymorphism and 3020InsC NOD2/CARD15 mutations. In smoker patients carrying the CX3CR1 allele I249, there was a significant increase in the frequency of fibrostenosing disease [P=0.005, odds ratio (OR): 3.25] whereas this relationship disappeared in the group of nonsmokers (P=0.72). In multivariate analysis, 3020InsC NOD2/CARD15 mutations and the V249I CX3CR1 polymorphism were independent risk factors for intestinal stenosis (P=0.046, OR: 1.8 and P=0.044, OR: 2.4, respectively).


CONCLUSIONS
In Crohn's disease, V249I CX3CR1 polymorphism is associated with intestinal strictures, particularly in smokers. This association is independent of CARD15 mutations.
Sabate
Jean-Marc
JM
Department of Gastroenterology and Hepatology, AP-HP, Louis Mourier Hospital, Colombes, France.
Ameziane
Nejma
N
Lamoril
Jérôme
J
Jouet
Pauline
P
Farmachidi
Jean-Pierre
JP
Soulé
Jean-Claude
JC
Harnois
Florence
F
Sobhani
Iradj
I
Jian
Raymond
R
Deybach
Jean-Charles
JC
de Prost
Dominique
D
Coffin
Benoit
B
D000328:Adult; D017668:Age of Onset; D000073883:CX3C Chemokine Receptor 1; D003424:Crohn Disease / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007415:Intestinal Obstruction / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D019707:Receptors, Chemokine / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D019707:Receptors, Chemokine