ANALYSIS OF CANDIDATE GENES ON CHROMOSOMES 5q AND 19p IN COELIAC DISEASE.

BACKGROUND AND AIM: Celiac disease (CD) is a multifactorial disease with involvement of both environmental and genetic susceptibility factors. The HLA-DQ loci account for 2000 CD patients and 4000 control individuals) question the role of MYO9B at the CELIAC4 locus as a disease-causing gene. Moreover, none of the investigated SNPs explain the linkage at the CELIAC2 locus

The association of MYO9B gene in Italian patients with inflammatory bowel diseases

Background Variants of myosin IXB (MY09B) gene, encoding for a motor protein implicated in epithelial permeability, have been recently associated with inflammatory bowel disease. Aims To investigate the contribution of three polymorphisms of MY09B gene for predisposition to Crohn's disease and ulcerative colitis, their association with clinical phenotypes, particularly intestinal permeability, and possible interaction with the CARD15 gene. Methods 549 Crohn's disease patients, 658 ulcerative colitis patients and 674 controls were genotyped for the rs962917, rs1545620 and rs2305764 single nucleotide polymorphisms. Results Highly significant genotypic association with Crohn's disease and ulcerative colitis was shown for all three single nucleotide polymorphisms, with odds ratio ranging from 1.5 to 1.7 (P-value: <0.01 to <0.002). A significant difference in allele frequencies was also observed in inflammatory bowel disease patients, with the single most significant association for rs1545620, detected in 47% of Crohn's disease, 47% of ulcerative colitis patients and 42% of controls (P < 0.005). No association with specific sub-phenotypes was found, with the exception of a trend towards an abnormal intestinal permeability (P = 0.043) in Crohn's disease carrying the rs1545620 risk allele. Conclusions Our findings confirm the association between the MY09B polymorphisms and susceptibility to both ulcerative colitis and Crohn's disease, with a weak influence on sub-phenotypic expression

Role of CARD15, DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases

Abstract 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