title: Prevalence of mutations of the NOD2/CARD15 gene and relation to phenotype in Spanish patients with Crohn disease.
abstract: BACKGROUND
  We assessed the prevalence of R702W, G908R, and L1007fs coding mutations in the NOD2/CARD15 gene and the genotype-phenotype relation in Spanish patients with Crohn disease.
  
  
  METHODS
  A cohort of 204 unrelated patients with Crohn disease and 140 healthy controls were studied. The phenotype was established before commencement of genotyping. Genotyping of the R702W, G908R, and L1007fs gene polymorphisms of NOD2/CARD15 was performed by two independent laboratories using different techniques. In the case of discordant results, specific sequencing of DNA strands was performed.
  
  
  RESULTS
  At least one mutation was present in 32.8% of patients compared to 10.7% in controls (OR = 4.08, 95% CI 2.21 to 7.50). In patients with Crohn disease, the frequency of R702W, G908R, and L1007fs carriers was 13.7%, 8.3%, and 14.2%, respectively. Compound heterozygotes and homozygotes occurred in 3.4% and 2.9% of patients and in none of the controls. The correlation of genotype-Vienna classification showed a significant association with ileal disease (RR = 1.61, 95% CI 1.21-2.15, P = 0.001) and an inverse association with colonic localization (RR = 0.29, 95% CI 0.11-0.80, P = 0.007). There was a significant association between G908R carriership and previous appendectomy, surgical interventions, and stricturing behavior. A gene-dosage effect on phenotypic characteristics was not observed.
  
  
  CONCLUSIONS
  In a Spanish population from Madrid, mutations of the NOD2/CARD15 gene were a marker of susceptibility to Crohn disease and were associated with ileal disease. Carriers of the G908R mutation showed a stricturing disease behavior, history of appendectomy, and surgical interventions over the course of the disease.
authors.affiliation: Dept. of Gastroenterology, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain. jmendozah@meditex.es
authors.forename: J L
authors.initials: JL
authors.lastname: Mendoza
authors.forename: L S
authors.initials: LS
authors.lastname: Murillo
authors.forename: L
authors.initials: L
authors.lastname: Fernández
authors.forename: A S
authors.initials: AS
authors.lastname: Peña
authors.forename: R
authors.initials: R
authors.lastname: Lana
authors.forename: E
authors.initials: E
authors.lastname: Urcelay
authors.forename: D M
authors.initials: DM
authors.lastname: Cruz-Santamaría
authors.forename: E G
authors.initials: EG
authors.lastname: de la Concha
authors.forename: M
authors.initials: M
authors.lastname: Díaz-Rubio
authors.forename: J
authors.initials: J
authors.lastname: García-Paredes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein; D010641:Phenotype; D011110:Polymorphism, Genetic; D013030:Spain
chemical_list: D002352:Carrier Proteins; D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein