Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease.
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.
Rigoli
Luciana
L
Dipartimento di Scienze Pediatriche Mediche e Chirurgiche, Policlinico Universitario, Messina 98125, Italy. luciana.rigoli@unime.it
Romano
Claudio
C
Caruso
Rosario Alberto
RA
Lo Presti
Maria A
MA
Di Bella
Chiara
C
Procopio
Vincenzo
V
Lo Giudice
Giuseppina
G
Amorini
Maria
M
Costantino
Giuseppe
G
Sergi
Maria D
MD
Cuppari
Caterina
C
Calabro
Giovanna Elisa
GE
Gallizzi
Romina
R
Salpietro
Carmelo Damiano
CD
Fries
Walter
W
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*
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4