The V249I polymorphism of the CX3CR1 gene is associated with fibrostenotic disease behavior in patients with Crohnʼs disease
| Autor: | Pauline Jouet, Jérôme Lamoril, Jean-Pierre Farmachidi, N. Ameziane, Benoit Coffin, Jean-Marc Sabate, Raymond Jian, Florence Harnois, Iradj Sobhani, Dominique de Prost, Soulé Jc, Jean-Charles Deybach |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Genotype CX3C Chemokine Receptor 1 Nod2 Signaling Adaptor Protein Disease Crohn Disease Risk Factors NOD2 CX3CR1 medicine Humans Genetic Predisposition to Disease Age of Onset Allele Retrospective Studies Crohn's disease Univariate analysis Polymorphism Genetic Hepatology business.industry Smoking Gastroenterology Odds ratio Middle Aged medicine.disease Phenotype digestive system diseases Mutation Immunology Female Receptors Chemokine business Intestinal Obstruction |
| Zdroj: | European Journal of Gastroenterology & Hepatology. 20:748-755 |
| ISSN: | 0954-691X |
| DOI: | 10.1097/meg.0b013e3282f824c9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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