Clinical Research
Copyright ©2007 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2007; 13(41): 5446-5453
Published online Nov 7, 2007. doi: 10.3748/wjg.v13.i41.5446
Influence of a nucleotide oligomerization domain 1 (NOD1) polymorphism and NOD2 mutant alleles on Crohn's disease phenotype
Elisabet Cantó, Elena Ricart, David Busquets, David Monfort, Esther García-Planella, Dolors González, Joaquim Balanzó, José L Rodríguez-Sánchez, Sílvia Vidal
Elisabet Cantó, José L Rodríguez-Sánchez, Sílvia Vidal, Department of Immunology, Sant Pau Hospital & Research Inst. Sant Pau Hospital, Barcelona 08025, Spain
Elena Ricart, Department of Gastroenterology, CIBER-EHD. Clinic Hospital, Barcelona-08025, Spain
David Busquets, David Monfort, Esther García-Planella, Dolors González, Joaquim Balanzó, Department of Digestive Pathology, Sant Pau Hospital, Barcelona 08025, Spain
Author contributions: All authors contributed equally to the work.
Supported by a grant of Ministerio Educacion y Ciencia (BFU 2006-15063); E.C. is participant of the Program "Contratos de apoyo a la Investigacion del Sistema Nacional de Salud". S.V. was supported by "Fondo Investigaciones Sanitarias" and participant of the Program for Stabilization of Investigators of "Direccio d' Estrategia i Coordinacio del Departament Salut de la Generalitat de Catalunya"
Correspondence to: Silvia Vidal, Department of Immunology, Institut Rec. Hospital Sant Pau, Avda. Antoni M. Claret, 167. Barcelona 08025, Spain. svidal@santpau.es
Telephone: +34-93-2919017 Fax: +34 -93-2919066
Received: July 4, 2007
Revised: August 17, 2007
Accepted: September 19, 2007
Published online: November 7, 2007
Abstract

AIM: 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: (ND1+32656*1) 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.

CONCLUSION: 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.

Keywords: Crohn's disease; Nucleotide oligomerization domain 1; Nucleotide oligomerization domain 2