Rigoli L, Romano C, Caruso RA, Presti MAL, Bella CD, Procopio V, Giudice GL, Amorini M, Costantino G, Sergi MD, Cuppari C, Calabrò GE, Gallizzi R, Salpietro CD, Fries W. Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease. World J Gastroenterol 2008; 14(28): 4454-4461 [PMID: 18680223 DOI: 10.3748/wjg.14.4454]
Corresponding Author of This Article
Luciana Rigoli, Dipartimento di Scienze Pediatriche Mediche e Chirurgiche, UO di Genetica ed Immunologia Pediatrica, pad. NI, Policlinico Universitario, Messina 98125, Italy. luciana.rigoli@unime.it
Article-Type of This Article
Clinical Research
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World J Gastroenterol. Jul 28, 2008; 14(28): 4454-4461 Published online Jul 28, 2008. doi: 10.3748/wjg.14.4454
Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease
Luciana Rigoli, Claudio Romano, Rosario Alberto Caruso, Maria A Lo Presti, Chiara Di Bella, Vincenzo Procopio, Giuseppina Lo Giudice, Maria Amorini, Giuseppe Costantino, Maria D Sergi, Caterina Cuppari, Giovanna Elisa Calabrò, Romina Gallizzi, Carmelo Damiano Salpietro, Walter Fries
Luciana Rigoli, Claudio Romano, Chiara Di Bella, Vincenzo Procopio, Giuseppina Lo Giudice, Maria Amorini, Caterina Cuppari, Giovanna Elisa Calabrò, Romina Gallizzi, Carmelo Damiano Salpietro, Dipartimento di Scienze Pediatriche Mediche e Chirurgiche, Università di Messina, Messina 98125, Italy
Rosario Alberto Caruso, Dipartimento di Patologia Umana, Università di Messina, Messina 98125, Italy
Maria A Lo Presti, Giuseppe Costantino, Maria D Sergi, Walter Fries, Dipartimento di Medicina Interna e Terapia Medica, Università di Messina, Messina 98125, Italy
Author contributions: Rigoli L, Romano C, Caruso RA and Fries W contributed equally to this work; Rigoli L, Romano C and Fries W designed research; Lo Presti MA, Di Bella C, Procopio V, Lo Giudice G, Amorini M, Costantino G, Sergi MD, Cuppari C, Calabrò GE, Gallizzi R performed research; Rigoli L and Salpietro CD contributed new reagents/analytic tools; Rigoli L, Romano C, Caruso RA and Fries W analyzed data; and Rigoli L wrote the paper.
Correspondence to: Luciana Rigoli, Dipartimento di Scienze Pediatriche Mediche e Chirurgiche, UO di Genetica ed Immunologia Pediatrica, pad. NI, Policlinico Universitario, Messina 98125, Italy. luciana.rigoli@unime.it
Telephone: +39-90-2212120
Fax: +39-90-2213788
Received: April 3, 2008 Revised: June 6, 2008 Accepted: June 13, 2008 Published online: July 28, 2008
Abstract
AIM: 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).
CONCLUSION: 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.
