References of "Pierik, M"
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See detailMixed IBD families: A distinct entity within IBD
Pierik, M.; Van Steen, Kristel ULg; Joossens, M. et al

in Gastroenterology (2007), 132(4), 450-450

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See detailNew serological markers in inflammatory bowel disease are associated with complicated disease behavior
Ferrante, M.; Henckaerts, L.; Joossens, M. et al

in Gut (2007), 56(10), 1394-1403

OBJECTIVE: The human androgen receptor (AR) contains a polyglutamine and a polyglycine stretch which are highly polymorphic and are coded respectively by a CAG and GGN repeat in exon 1 of the AR gene ... [more ▼]

OBJECTIVE: The human androgen receptor (AR) contains a polyglutamine and a polyglycine stretch which are highly polymorphic and are coded respectively by a CAG and GGN repeat in exon 1 of the AR gene. Although the in vitro studies indicated a possible effect of the GGN repeat polymorphism on the AR gene transcription and clinical observations suggest that it might modulate the androgen action, its functional significance remains unclear. We wanted to assess whether the GGN repeat affects the serum testosterone levels in healthy men, which is the expected outcome through feedback regulation if it influences androgen action as has been shown to be the case for the CAG repeat. DESIGN AND PATIENTS: A population based cross-sectional cohort study including 1476 healthy young, middle-aged, and elderly men. MEASUREMENT: Testosterone and LH levels were determined by immunoassay; free testosterone (FT) levels were calculated. Genotyping of the GGN repeat was performed using the sequencing technique. RESULTS: The GGN repeat number was significantly associated with circulating testosterone and FT levels (P=0.017 and P=0.013 respectively). However, taking into account that age, body mass index, and CAG are already in the regression model, the GGN repeat could explain only a small part of the variation of both testosterone and FT. CONCLUSION: To our knowledge, this study is the first to demonstrate a significant positive association between the GGN repeat and androgen levels in a large cohort of healthy men. Although the present study thus adds credence to the view that the polyglycine tract in the AR can modulate AR action, this effect appears to be only small so that its clinical relevance remains questionable. [less ▲]

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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 detailPancreatic autoantibodies in inflammatory bowel disease
Joossens, S.; Vermeire, S.; Van Steen, Kristel ULg et al

in Inflammatory Bowel Diseases (2004), 10(6), 771-777

Background: Autoantibodies against exocrine pancreas (PABs) have been reported to be specific for Crohn's disease (CD), albeit at a low prevalence (30%). We studied PABs in patients with inflammatory ... [more ▼]

Background: Autoantibodies against exocrine pancreas (PABs) have been reported to be specific for Crohn's disease (CD), albeit at a low prevalence (30%). We studied PABs in patients with inflammatory bowel disease (IBD), unaffected family members, and control subjects. Methods: A Belgian study cohort of 575 subjects, including 289 IBD patients (CD, 169 patients; ulcerative colitis [UC], 120 patients), 108 unaffected first-degree relatives, 78 subjects with non-IBD gastrointestinal disorders (gastrointestinal control subjects [GIcos]), and 100 healthy control subjects (Hcos), were tested for PAB by a standardized indirect immunofluorescence method. Results: The prevalence of PABs in this study cohort was 32% for CD, 23.3% for UC, and 22.2% for their unaffected family members (all P < 0.001), compared with 1.3% for GIcos and 0% for Hcos. Two staining patterns could be observed: an intracellular pattern (IC); and an extracellular pattern (EC). The EC was significantly more prevalent in CD patients compared with UC patients (P = 0.014), and higher titers of this pattern were found in CD patients (P = 0.01). Both PAB patterns were negatively associated with stricturing disease behavior of CD (P = 0.021). The IC was associated with familial CD (P = 0.0009) and familial UC (P = 0.0003). Conclusions: The prevalence of PAB found in CD patients in this study was similar to that cited in previous reports. In contrast to these reports, we also found an increased prevalence of PABs in patients with UC and in unaffected first-degree relatives of IBD patients. We observed two main staining patterns, both of which were present in IBD and were associated with specific phenotypes of the disease. [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 detailDeficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis
Franchimont, D.; Vermeire, S.; El Housni, H. et al

in Gut (2004), 53(7), 987-992

Background and aims: Elicitation of an innate immune response to bacterial products is mediated through pattern recognition receptors (PRRs) such as the toll-like receptors (TLRs) and the NODs. The ... [more ▼]

Background and aims: Elicitation of an innate immune response to bacterial products is mediated through pattern recognition receptors (PRRs) such as the toll-like receptors (TLRs) and the NODs. The recently characterised Asp299Gly polymorphism in the lipopolysaccharide (LPS) receptor TLR4 is associated with impaired LPS signalling and increased susceptibility to Gram negative infections. We sought to determine whether this polymorphism was associated with Crohn's disease ( CD) and/or ulcerative colitis (UC). Methods: Allele frequencies of the TLR4 Asp299Gly polymorphism and the three NOD2/CARD15 polymorphisms (Arg702Trp, Gly908Arg, and Leu1007fsinsC) were assessed in two independent cohorts of CD patients ( cohort 1, n = 334; cohort 2, n = 114), in 163 UC patients, and in 140 controls. A transmission disequilibrium test (TDT) was then performed on 318 inflammatory bowel disease (IBD) trios. Results: The allele frequency of the TLR4 Asp299Gly polymorphism was significantly higher in CD ( cohort 1: 11% v 5%, odds ratio ( OR) 2.31 (95% confidence interval (CI) 1.28 - 4.17), p = 0.004; and cohort 2: 12% v 5%, OR 2.45 ( 95% CI 1.24 - 4.81), p = 0.007) and UC patients (10% v 5%, OR 2.05 ( 95% CI 1.07 3.93), p = 0.027) compared with the control population. A TDT on 318 IBD trios demonstrated preferential transmission of the TLR4 Asp299Gly polymorphism from heterozygous parents to affected children (T/U: 68/34, p = 0.01). Carrying polymorphisms in both TLR4 and NOD2 was associated with a genotype relative risk (RR) of 4.7 compared with a RR of 2.6 and 2.5 for TLR4 and NOD2 variants separately. Conclusion: We have reported on a novel association of the TLR4 Asp299Gly polymorphism with both CD and UC. This finding further supports the genetic influence of PRRs in triggering IBD. [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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