AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predisposition 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 parents (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 < 0.001). Homozygosis for both OCTN1/2 variants was more common in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an increased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the 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 more frequent (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 onset of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype.
AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predisposition 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 parents (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 < 0.001). Homozygosis for both OCTN1/2 variants was more common in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an increased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the 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 more frequent (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 onset of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype.
Authors: J D Rioux; M J Daly; M S Silverberg; K Lindblad; H Steinhart; Z Cohen; T Delmonte; K Kocher; K Miller; S Guschwan; E J Kulbokas; S O'Leary; E Winchester; K Dewar; T Green; V Stone; C Chow; A Cohen; D Langelier; G Lapointe; D Gaudet; J Faith; N Branco; S B Bull; R S McLeod; A M Griffiths; A Bitton; G R Greenberg; E S Lander; K A Siminovitch; T J Hudson Journal: Nat Genet Date: 2001-10 Impact factor: 38.330
Authors: Muddassar M Mirza; Sheila A Fisher; Kathy King; Andrew P Cuthbert; Jochen Hampe; Jeremy Sanderson; John Mansfield; Peter Donaldson; Andrew J S Macpherson; Alastair Forbes; Stefan Schreiber; Cathryn M Lewis; Christopher G Mathew Journal: Am J Hum Genet Date: 2003-03-03 Impact factor: 11.025
Authors: C Gasche; J Scholmerich; J Brynskov; G D'Haens; S B Hanauer; E J Irvine; D P Jewell; D Rachmilewitz; D B Sachar; W J Sandborn; L R Sutherland Journal: Inflamm Bowel Dis Date: 2000-02 Impact factor: 5.325
Authors: J P Hugot; M Chamaillard; H Zouali; S Lesage; J P Cézard; J Belaiche; S Almer; C Tysk; C A O'Morain; M Gassull; V Binder; Y Finkel; A Cortot; R Modigliani; P Laurent-Puig; C Gower-Rousseau; J Macry; J F Colombel; M Sahbatou; G Thomas Journal: Nature Date: 2001-05-31 Impact factor: 49.962
Authors: Y Ogura; D K Bonen; N Inohara; D L Nicolae; F F Chen; R Ramos; H Britton; T Moran; R Karaliuskas; R H Duerr; J P Achkar; S R Brant; T M Bayless; B S Kirschner; S B Hanauer; G Nuñez; J H Cho Journal: Nature Date: 2001-05-31 Impact factor: 49.962
Authors: K Negoro; D P B McGovern; Y Kinouchi; S Takahashi; N J Lench; T Shimosegawa; A Carey; L R Cardon; D P Jewell; D A van Heel Journal: Gut Date: 2003-04 Impact factor: 23.059
Authors: E Louis; V Michel; J P Hugot; C Reenaers; F Fontaine; M Delforge; F El Yafi; J F Colombel; J Belaiche Journal: Gut Date: 2003-04 Impact factor: 23.059
Authors: Josef Wagner; Winnie H Sim; Justine A Ellis; Eng K Ong; Anthony G Catto-Smith; Donald J S Cameron; Ruth F Bishop; Carl D Kirkwood Journal: PLoS One Date: 2010-11-08 Impact factor: 3.240