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Role of CARD15,dlg5 and OCTN genes polymorphisms in children with inflammatory bowel diseases

World Journal of Gastroenterology 2007年第8期13卷 1221-1229页

作者： S Cucchiara A Latiano O Palmieri AM Staiano R D'Incà G Guariso G Vieni V Rutigliano O Borrelli MR Valvano V Annese Clinica Pediatrica Università "La Sapienza" Roma Italy U.O. Gastroenterologia IRCCS "Casa Sollievo della Sofferenza" San Giovanni Rotondo Italy Clinica Pediatrica Università di Napoli Università di Padova Italy Cattedra di Gastroenterologia Università di Padova Italy Clinica Pediatrica Università di Padova Italy Clinica Pediatrica Università di Messina Italy Clinica Pediatrica Università di Bari Italy

AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and dlg5 genes in disease predispo- sition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). METHODS: Two hundred patients with Crohn’s disease (CD), 186 ulcerative colitis (UC) patients, 434 par- ents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes, IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the dlg5 gene were evaluated. Potential correlations with clinical sub-phenotypes were investigated. RESULTS: Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P dlg5 variant was found. CD carriers of OCTN1/2 and dlg5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was morefrequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed. CONCLUSION: Polymorphisms of CARD15 and OCTN genes, but not dlg5 are associated with pediatric on- set of CD. Polymorphisms of CARD15, OCTN, and dlg5 genes exert a weak influence on CD phenotype.

关键词： Inflammatory bowel disease Ulcerative colitis Crohn's disease CARD15 dlg5, carnitine/organic cation transporter gene

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