title: Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease.
abstract: OBJECTIVE
  To evaluate the role of genetic factors in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC), we investigated the single nucleotide polymorphisms (SNPs) of NOD2/CARD15 (R702W, G908R and L1007finsC), and Toll-like receptor 4 (TLR4) genes (D299G and T399I) in a selected inflammatory bowel disease (IBD) population coming from Southern Italy.
  
  
  METHODS
  Allele and genotype frequencies of NOD2/CARD15 (R702W, G908R and L1007finsC) and TLR4 (D299G and T399I) SNPs were examined in 133 CD patients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed.
  
  
  RESULTS
  NOD2/CARD15 R702W mutation was significantly more frequent in CD (9.8%) than in controls (2.4%, P = 0.001) and in UC (2.3%, P = 0.03). No significant difference was found between UC patients and control group (P > 0.05). In CD and UC patients, no significant association with G908R variant was found. L1007finsC SNP showed an association with CD (9.8%) compared with controls (2.9%, P = 0.002) and UC patients (2.3%, P = 0.01). Moreover, in CD patients, G908R and L1007finsC mutations were significantly associated with different phenotypes compared to CD wild-type patients. No association of IBD with the TLR4 SNPs was found in either cohort (allele frequencies: D299G-controls 3.9%, CD 3.7%, UC 3.4%, P > 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P > 0.05).
  
  
  CONCLUSIONS
  These findings confirm that, in our IBD patients selected from Southern Italy, the NOD2/CARD15, but not TLR4 SNPs, are associated with increased risk of CD.
authors.affiliation: Dipartimento di Scienze Pediatriche Mediche e Chirurgiche, Policlinico Universitario, Messina 98125, Italy. luciana.rigoli@unime.it
authors.forename: Luciana
authors.initials: L
authors.lastname: Rigoli
authors.forename: Claudio
authors.initials: C
authors.lastname: Romano
authors.forename: Rosario Alberto
authors.initials: RA
authors.lastname: Caruso
authors.forename: Maria A
authors.initials: MA
authors.lastname: Lo Presti
authors.forename: Chiara
authors.initials: C
authors.lastname: Di Bella
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Procopio
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Lo Giudice
authors.forename: Maria
authors.initials: M
authors.lastname: Amorini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Costantino
authors.forename: Maria D
authors.initials: MD
authors.lastname: Sergi
authors.forename: Caterina
authors.initials: C
authors.lastname: Cuppari
authors.forename: Giovanna Elisa
authors.initials: GE
authors.lastname: Calabro
authors.forename: Romina
authors.initials: R
authors.lastname: Gallizzi
authors.forename: Carmelo Damiano
authors.initials: CD
authors.lastname: Salpietro
authors.forename: Walter
authors.initials: W
authors.lastname: Fries
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D003424:Crohn Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4