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See detailGenetic markers and the risk of complicated disease behaviour in Crohn’s disease patients
Henckaerts, L.; Verstreken, I.; Van Steen, Kristel ULg et al

in Gut (2007)

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See detailGenetic markers and the risk of complicated disease behaviour in Crohn's disease patients
Henckaerts, L.; Verstreken, I.; Van Steen, Kristel ULg et al

in Gastroenterology (2007), 132(4), 17-18

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See detailToll-like receptor-1,-2, and-6 polymorphisms influence disease extension in inflammatory bowel diseases
Pierik, M.; Joossens, S.; Van Steen, Kristel ULg et al

in Inflammatory Bowel Diseases (2006), 12(1), 1-8

Background: Evidence that a deficient innate immune response toward the bacterial flora of the gut plays a role in the pathogenesis of inflammatory bowel disease (IBD) is growing. This is underscored by ... [more ▼]

Background: Evidence that a deficient innate immune response toward the bacterial flora of the gut plays a role in the pathogenesis of inflammatory bowel disease (IBD) is growing. This is underscored by the finding of the association between CARD15 variants and Crohn's disease (CD) and D299G in Toll-like receptor (TLR) 4 and IBD. Our aims were to study nonsynonymous polymorphisms in other TLR genes in IBD. Methods: Thirty-five single nucleotide polymorphisms (SNP) in TLR1-10 were identified from public databases. 284 IBD parent child trios and a second independent cohort of 285 IBD patients and 191 healthy controls were genotyped with polymerase chain reaction-restriction fragment length polymorphisms. Patients were pooled for genotype-phenotype analyses. Results: Although none of the SNPs was involved in disease susceptibility, a number of variants influenced the disease phenotype. A positive association between TLR1 R80T and pancolitis in UC (P = .045, OR [95% CI] 2.844 [1.026-7.844]) was found. The TLR2 R753G SNP was also associated with pancolitis (P = .027, OR [95% CI] 4.741 [1.197-18.7731). The relative risks for heterozygous patients to develop pancolitis were 5.8 and 3.3 for R80T and R753G, respectively. There was a negative association between TLR6 S249P and ulcerative colitis with proctitis only (P = .026, OR [95% CI] 0.223 [0.096-0.705]). In CD, we found a negative association between ileal disease involvement and TLR1 S6021 (P = .03, OR [95% CI] 0.522 [0.286-0.950]). Conclusion: TLR2 and its cofactors TLR1 and TLR6 are involved in the initial immune response to bacteria by recognizing peptidoglycan. An association between nonsynonymous variants in the TLR1, -2, and -6 genes and extensive colonic disease in UC and CD was found. Our findings further highlight the role of an abnormal innate immune response in the pathogenesis of IBD. [less ▲]

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See detailTumour necrosis factor- receptor 1 and 2 polymorhpisms in inflammatory bowel disease and their association with response to infliximab
Pierik, M.; Vermeire, S.; Van Steen, Kristel ULg et al

in Alimentary Pharmacology & Therapeutics (2004), 20

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See detailGenome wide scan in a Flemish inflammatory bowel disease population: support for the IBD4 locus, population heterogeneity, and epistasis
Vermeire, S.; Rutgeerts, P.; Van Steen, Kristel ULg et al

in Gut (2004), 53(7), 980-986

Background and aims: Genome wide scans in inflammatory bowel disease (IBD) have indicated various susceptibility regions with replication of 16cen (IBD1), 12q (IBD2), 6p (IBD3), 14q11 (IBD4), and 3p21. As ... [more ▼]

Background and aims: Genome wide scans in inflammatory bowel disease (IBD) have indicated various susceptibility regions with replication of 16cen (IBD1), 12q (IBD2), 6p (IBD3), 14q11 (IBD4), and 3p21. As no linkage was previously found on IBD regions 3, 7, 12, and 16 in Flemish IBD families, a genome wide scan was performed to detect other susceptibility regions in this population. Methods: A cohort of 149 IBD affected relative pairs, all recruited from the Northern Flemish part of Belgium, were genotyped using microsatellite markers at 12 cM intervals, and analysed by Genehunter non-parametric linkage software. All families were further genotyped for the three main Crohn's disease associated variants in the NOD2/CARD15 gene. Results: Nominal evidence for linkage was observed on chromosomes 1 (D1S197: multipoint nonparametric linkage (NPL) score 2.57, p = 0.004; and at D1S305-D1S252: NPL 2.97, p = 0.001), 4q (D4S406: NPL 1.95, p = 0.03), 6q16 (D6S314: NPL 2.44, p = 0.007), 10p12 (D10S197: NPL 2.05, p = 0.02), 11q22 (D11S35-D11S927: NPL 1.95, p = 0.02) 14q11-12 (D14S80: NPL 2.41, p = 0.008), 20p12 (D20S192: NPL 2.7, p = 0.003), and Xq (DXS990: NPL 1.70, p = 0.04). A total of 51.4% of patients carried at least one NOD2/CARD15 variant. Furthermore, epistasis was observed between susceptibility regions 6q/10p and 20p/10p. Conclusion: Genome scanning in a Flemish IBD population found nominal evidence for linkage on 1p, 4q, 10p12, and 14q11, overlapping with other genome scan results, with linkage on 14q11-12 supporting the IBD4 locus. The results further show that epistasis is contributing to the complex model of IBD and indicate that population heterogeneity is not to be underestimated. Finally, NOD2/CARD15 is clearly implicated in the Flemish IBD population. [less ▲]

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See detailTransmission of CARD15 (NOD2) variants in families with Crohns disease
Vermeire, S.; Esters, N.; Pierik, M. et al

in Gastroenterology (2003), 124(4 (Suppl I)), 368

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See detailNOD2/CARD15 does not influence response to infliximab in Crohn's disease
Vermeire, S.; Louis, Edouard ULg; Rutgeerts, P. et al

in Gastroenterology (2002), 123(1), 106-111

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