The V249I polymorphism of the CX3CR1 gene is associated with fibrostenotic disease behavior in patients with Crohn's disease.

Objectives: 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).

Conclusion: In Crohn's disease, V249I CX3CR1 polymorphism is associated with intestinal strictures, particularly in smokers. This association is independent of CARD15 mutations.