title: Influence of a nucleotide oligomerization domain 1 (NOD1) polymorphism and NOD2 mutant alleles on Crohn's disease phenotype.
abstract: OBJECTIVE
  To examine genetic variation of nucleotide oligomerization domain 1 (NOD1) and NOD2, their respective influences on Crohn's disease phenotype and gene-gene interactions.
  
  
  METHODS
  (ND(1)+32656*) NOD1 polymorphism and SNP8, SNP12 and SNP13 of NOD2 were analyzed in 97 patients and 50 controls. NOD2 variants were determined by reaction restriction fragment length polymorphism analysis. NOD1 genotyping and NOD2 variant confirmation were performed by specific amplification and sequencing.
  
  
  RESULTS
  The distribution of NOD1 polymorphism in patients was different from controls (P = 0.045) and not altered by existence of NOD2 mutations. In this cohort, 30.92% patients and 6% controls carried at least one NOD2 variant (P < 0.001) with R702W being the most frequent variant. Presence of at least one NOD2 mutation was inversely associated with colon involvement (9.09% with colon vs 36.4% with ileal or ileocolonic involvement, P = 0.04) and indicative of risk of penetrating disease (52.63% with penetrating vs 25.64% with non-penetrating or stricturing behavior, P = 0.02). L1007finsC and double NOD2 mutation conferred the highest risk for severity of disease (26.3% with penetrating disease vs 3.8% with non-penetrating or stricturing behavior presented L1007finsC, P = 0.01 and 21.0% with penetrating disease vs 2.5% with non-penentrating or stricturing behavior carried double NOD2 mutation, P = 0.007). Exclusion of patients with NOD2 mutations from phenotype/NOD1-genotype analysis revealed higher prevalence of *1*1 genotype in groups of younger age at onset and colonic location.
  
  
  CONCLUSIONS
  This study suggests population differences in the inheritance of risk NOD1 polymorphism and NOD2 mutations. Although no interaction between NOD1-NOD2 was noticed, a relationship between disease location and Nod-like receptor molecules was established.
authors: Department of Immunology, Sant Pau Hospital & Research Inst. Sant Pau Hospital, Barcelona 08025, Spain.
authors: Elisabet
authors: E
authors: Cantó
authors: Elena
authors: E
authors: Ricart
authors: David
authors: D
authors: Busquets
authors: David
authors: D
authors: Monfort
authors: Esther
authors: E
authors: García-Planella
authors: Dolors
authors: D
authors: González
authors: Joaquim
authors: J
authors: Balanzó
authors: José-L
authors: JL
authors: Rodriguez-Sanchez
authors: Sílvia
authors: S
authors: Vidal
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003106:Colon / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007082:Ileum / Q000473:pathology; D009154:Mutation; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein