References of "Van Steen, Kristel"
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See detailReanalysis of death risk in long-term follow-up in infliximab patients versus controls
Fidder, H.; Van Steen, Kristel ULg; Van Assche, G. et al

in Gut (2010), 59

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See detailIntestinal mucosal expression of matrix metalloproteinase and ADAM genes in patients with inflammatory bowel disease and the impact of infliximab therapy
Arijs, Ingrid; Quintens, R.; Lemaire, K. et al

in Gastroenterology (2010), 138(5), 677

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See detailImmortal time bias and infliximab-related mortality and malignancy incidence
Fidder, H.; Van Steen, Kristel ULg; Van Assche, G. et al

in Gut (2010), 59

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See detailColonic mucosal expression of barrier genes in patients with inflammatory bowel disease before and after first infliximab treatmen
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

in Acta Gastro-Enterologica Belgica (2009)

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See detailSelecting multiple epistatic models using MB-MDR
Cattaert, Tom ULg; De Wit, V.; Mahachie John, Jestinah ULg et al

in Conference Abstract Book (2009)

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See detailGENESTAT: an information portal for design and analysis of genetic association studies
Ripatti, Samuli; Becker, Tim; Bickeboller, Heike et al

in European Journal of Human Genetics (2009), 17(4), 533-6

We present the rationale, the background and the structure for version 2.0 of the GENESTAT information portal (www.genestat.org) for statistical genetics. The fast methodological advances, coupled with a ... [more ▼]

We present the rationale, the background and the structure for version 2.0 of the GENESTAT information portal (www.genestat.org) for statistical genetics. The fast methodological advances, coupled with a range of standalone software, makes it difficult for expert as well as non-expert users to orientate when designing and analysing their genetic studies. The ultimate ambition of GENESTAT is to guide on statistical methodology related to the broad spectrum of research in genetic epidemiology. GENESTAT 2.0 focuses on genetic association studies. Each entry provides a summary of a topic and gives links to key papers, websites and software. The flexibility of the internet is utilised for cross-referencing and for open editing. This paper gives an overview of GENESTAT and gives short introductions to the current main topics in GENESTAT, with additional entries on the website. Methods and software developers are invited to contribute to the portal, which is powered by a Wikipedia-type engine and allows easy additions and editing. [less ▲]

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See detailCluster analysis of genetic variants enables reclassification of Crohn’s disease at the molecular level
Cleynen, I.; Van Moerkercke, W.; Mahachie John, Jestinah ULg et al

in Gut (2009)

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See detailImportin-13 genetic variation is associated with improved airway responsiveness in childhood asthma
Raby, B. A.; Van Steen, Kristel ULg; Lasky-Su, J. et al

in Respiratory Research (2009), 10

BACKGROUND: Glucocorticoid function is dependent on efficient translocation of the glucocorticoid receptor (GR) from the cytoplasm to the nucleus of cells. Importin-13 (IPO13) is a nuclear transport ... [more ▼]

BACKGROUND: Glucocorticoid function is dependent on efficient translocation of the glucocorticoid receptor (GR) from the cytoplasm to the nucleus of cells. Importin-13 (IPO13) is a nuclear transport receptor that mediates nuclear entry of GR. In airway epithelial cells, inhibition of IPO13 expression prevents nuclear entry of GR and abrogates anti-inflammatory effects of glucocorticoids. Impaired nuclear entry of GR has been documented in steroid-non-responsive asthmatics. We hypothesize that common IPO13 genetic variation influences the anti-inflammatory effects of inhaled corticosteroids for the treatment of asthma, as measured by change in methacholine airway hyperresponsiveness (AHR-PC20). METHODS: 10 polymorphisms were evaluated in 654 children with mild-to-moderate asthma participating in the Childhood Asthma Management Program (CAMP), a clinical trial of inhaled anti-inflammatory medications (budesonide and nedocromil). Population-based association tests with repeated measures of PC20 were performed using mixed models and confirmed using family-based tests of association. RESULTS: Among participants randomized to placebo or nedocromil, IPO13 polymorphisms were associated with improved PC20 (i.e. less AHR), with subjects harboring minor alleles demonstrating an average 1.51-2.17 fold increase in mean PC20 at 8-months post-randomization that persisted over four years of observation (p = 0.01-0.005). This improvement was similar to that among children treated with long-term inhaled corticosteroids. There was no additional improvement in PC20 by IPO13 variants among children treated with inhaled corticosteroids. CONCLUSION: IPO13 variation is associated with improved AHR in asthmatic children. The degree of this improvement is similar to that observed with long-term inhaled corticosteroid treatment, suggesting that IPO13 variation may improve nuclear bioavailability of endogenous glucocorticoids. [less ▲]

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See detailMucosal gene signatures to predict response to infliximab in patients with ulcerative colitis
Arijs, I.; Li, K.; Toedter, G. et al

in Gut (2009), 58(12), 1612-9

BACKGROUND AND AIMS: Infliximab is an effective treatment for ulcerative colitis with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti ... [more ▼]

BACKGROUND AND AIMS: Infliximab is an effective treatment for ulcerative colitis with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-tumour necrosis factor alpha (anti-TNFalpha) is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in ulcerative colitis. METHODS: Two cohorts of patients who received their first treatment with infliximab for refractory ulcerative colitis were studied. Response to infliximab was defined as endoscopic and histological healing. Total RNA from pre-treatment colonic mucosal biopsies was analysed with Affymetrix Human Genome U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data. RESULTS: For predicting response to infliximab treatment, pre-treatment colonic mucosal expression profiles were compared for responders and non-responders. Comparative analysis identified 179 differentially expressed probe sets in cohort A and 361 in cohort B with an overlap of 74 probe sets, representing 53 known genes, between both analyses. Comparative analysis of both cohorts combined, yielded 212 differentially expressed probe sets. The top five differentially expressed genes in a combined analysis of both cohorts were osteoprotegerin, stanniocalcin-1, prostaglandin-endoperoxide synthase 2, interleukin 13 receptor alpha 2 and interleukin 11. All proteins encoded by these genes are involved in the adaptive immune response. These markers separated responders from non-responders with 95% sensitivity and 85% specificity. CONCLUSION: Gene array studies of ulcerative colitis mucosal biopsies identified predictive panels of genes for (non-)response to infliximab. Further study of the pathways involved should allow a better understanding of the mechanisms of resistance to infliximab therapy in ulcerative colitis. ClinicalTrials.gov number, NCT00639821. [less ▲]

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See detailPredictive Value of C-Reactive Protein Level Changes On the Long Term Outcome of Infliximab in Crohn's Disease
Jürgens, M.; Schnitzler, F.; Van Steen, Kristel ULg et al

in Gastroenterology (2009), 136(5), 171

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See detailGenetic risk profiling and prediction of disease course in Crohn's disease patients.
Henckaerts, Liesbet; Van Steen, Kristel ULg; Verstreken, Isabel et al

in Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of The American Gastroenterological Association (2009), 7(9), 972-9802

BACKGROUND & AIMS: Clinical presentation at diagnosis and disease course of Crohn's disease (CD) are heterogeneous and variable over time. Early introduction of immunomodulators and/or biologicals might ... [more ▼]

BACKGROUND & AIMS: Clinical presentation at diagnosis and disease course of Crohn's disease (CD) are heterogeneous and variable over time. Early introduction of immunomodulators and/or biologicals might be justified in patients at risk for disease progression, so it is important to identify these patients as soon as possible. We examined the influence of recently discovered CD-associated susceptibility loci on changes in disease behavior and evaluated whether a genetic risk model for disease progression could be generated. METHODS: Complete medical data were available for 875 CD patients (median follow-up time, 14 years; interquartile range, 7-22). Fifty CD-associated polymorphisms were genotyped. Kaplan-Meier survival analyses, multiple logistic regression, and generalized multifactor dimensionality reduction analyses (GMDR) were performed, correcting for follow-up time. RESULTS: Homozygosity for the rs1363670 G-allele in a gene encoding a hypothetical protein near the IL12B gene was independently associated with stricturing disease behavior (odds ratio [OR], 5.48; 95% confidence interval [CI], 1.60-18.83; P = .007) and with shorter time to strictures (P = .01), especially in patients with ileal involvement (P = .0002). Male patients carrying at least one rs12704036 T-allele in a gene desert had the shortest time to non-perianal fistula (P < .0001). The presence of a C-allele at the CDKAL1 single nucleotide polymorphism rs6908425 and the absence of NOD2 variants were independently associated with development of perianal fistula (OR, 8.86; 95% CI, 1.13-69.78; P = .04 and OR, 0.56; 95% CI, 0.38-0.83; P = .004, respectively), particularly when colonic involvement and active smoking were present. CONCLUSIONS: CD-associated polymorphisms play a role in disease progression and might be useful in identifying patients who could benefit from an early top-down treatment approach. [less ▲]

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See detailThe impact of infliximab therapy on colonic mucosal expression of barrier genes in patients with inflammatory bowel disease
Arijs, I.; Quintens, R.; Van Lommel, L. et al

in Gastroenterology (2009), 136

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See detailLong-term outcome of treatment with infliximab in 614 patients with Crohn's disease: results from a single-centre cohort
Schnitzler, F.; Fidder, H.; Ferrante, M. et al

in Gut (2009), 58(4), 492-500

BACKGROUND AND AIMS: This observational study assessed the long-term clinical benefit of infliximab (IFX) in 614 consecutive patients with Crohn's disease (CD) from a single centre during a median follow ... [more ▼]

BACKGROUND AND AIMS: This observational study assessed the long-term clinical benefit of infliximab (IFX) in 614 consecutive patients with Crohn's disease (CD) from a single centre during a median follow-up of 55 months (interquartile range (IQR) 27-83). METHODS: The primary analysis looked at the proportion of patients with initial response to IFX who had sustained clinical benefit at the end of follow-up. The long-term effects of IFX on the course of CD as reflected by the rate of surgery and hospitalisations and need for corticosteroids were also analysed. RESULTS: 10.9% of patients were primary non-responders to IFX. Sustained benefit was observed in 347 of the 547 patients (63.4%) receiving long-term treatment. In 68.3% of these, treatment with IFX was ongoing and in 31.7% IFX was stopped, with the patient being in remission. Seventy patients (12.8%) had to stop IFX due to side effects and 118 (21.6%) due to loss of response. Although the yearly drop-out rates of IFX in patients with episodic (10.7%) and scheduled treatment (7.1%) were similar, the need for hospitalisations and surgery decreased less in the episodic than in the scheduled group. Steroid discontinuation also occurred in a higher proportion of patients in the scheduled group than in the episodic group. CONCLUSIONS: In this large real-life cohort of patients with CD, long-term treatment with IFX was very efficacious to maintain improvement during a median follow-up of almost 5 years and changed disease outcome by decreasing the rate of hospitalisations and surgery. [less ▲]

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See detailColonic mucosal expression of barrier genes in patients with inflammatory bowel disease before and after first infliximab treatment.
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

in Journal of Crohn’s and Colitis [=JCC] (2009), 3(1), 3

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See detailPredictive Value of C-Reactive Protein Level Changes On the Long Term Outcome of Infliximab in Crohn's Disease
Jürgens, M.; Schnitzler, F.; Van Steen, Kristel ULg et al

in Acta Gastro-Enterologica Belgica (2009)

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See detailSmall effect of the androgen receptor gene GGN repeat polymorphism on serum testosterone levels in healthy men
Bogaert, V.; Vanbillemont, G.; Taes, Y. et al

in European Journal of Endocrinology (2009), 161(1), 171-7

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 detailPolymorphisms of the SHBG gene contribute to the interindividual variation of sex steroid hormone blood levels in young, middle-aged and elderly men
Vanbillemont, G.; Bogaert, V.; De Bacquer, D. et al

in Clinical Endocrinology (2009), 70(2), 303-310

In men there is a large interindividual variation of SHBG levels and consequently of testosterone (T) and E-2 levels. Family and twin studies suggested a strong genetic contribution, besides metabolic and ... [more ▼]

In men there is a large interindividual variation of SHBG levels and consequently of testosterone (T) and E-2 levels. Family and twin studies suggested a strong genetic contribution, besides metabolic and hormonal influences. The aim of this study was to examine the influence of a missense mutation in exon 8 (Asp327Asn) and a (TAAAA)(n)-repeat in the promoter region of the SHBG gene, on SHBG and sex steroid serum concentrations in a population of healthy men. SHBG and hormone levels were measured in 1485 men, contributed by three independent cohort studies and representing three different age groups (young, middle-aged and elderly men). The number of TAAAA-repeats was determined by fragment-analysis; carriers of the Asn(327)-allele were identified using restriction fragment length polymorphism analysis. In the different age groups, carriers of six TAAAA-repeats presented with higher SHBG (young 19%, middle-aged 20% and elderly 26%; P < 0.001) and T (young 9%, middle-aged 22% and elderly 21%; P < 0.05) levels compared to non-carriers. For free T, a modest increase was found for carriers in the middle-aged group, but not for the young and elderly group. E-2 and free E-2 did not differ between carriers and non-carriers in the different age-groups. The Asn(327)-allele was associated with higher mean SHBG (14.20%, P < 0.001) and T levels (7.33%; P = 0.01) in the middle-aged group only. Our findings show that and the (TAAAA)(n)-repeat and the Asp327Asn polymorphism contribute to the genetically determined interindividual variation in total serum T levels in healthy men through variation in SHBG concentrations. [less ▲]

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See detailTECK and MADCAM-1 mucosal expression in active IBD: the effect of infliximab therapy
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

in Gastroenterology (2009), 136

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See detailA Family-Based Association Test to Detect Gene-Gene Interactions in the Presence of Linkage
De Lobel, L.; De Meyer, H.; Thijs, L. et al

in Genetic Epidemiology (2009), 33(8), 77168

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