References of "Henckaerts, L"
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See detailEffects of haptoglobin polymorphisms and deficiency on susceptibility to inflammatory bowel disease and on severity of murine colitis.
Marquez, L.; Shen, C.; Cleynen, I. et al

in Gut (2011), 61(4), 528-534

BackgroundHaptoglobin (Hp) is a haemoglobin-binding protein with immunomodulatory properties. Its gene (16q22) harbours a common polymorphism with two different alleles: Hp1 and Hp2. Genotype Hp22 has ... [more ▼]

BackgroundHaptoglobin (Hp) is a haemoglobin-binding protein with immunomodulatory properties. Its gene (16q22) harbours a common polymorphism with two different alleles: Hp1 and Hp2. Genotype Hp22 has been shown to be over-represented in different immune diseases. Results in Crohn's disease (CD) are contradictory.AimsTo determine whether Hp plays a role in inflammatory bowel disease, both genetically and functionally.Methods1061 patients with CD, 755 with ulcerative colitis (UC) and 152 with primary sclerosing cholangitis, as well as 452 healthy controls, were genotyped using touch-down PCR. To confirm association results, 464 CD trios and 151 UC trios were genotyped. Serum Hp concentrations were determined in 62 individuals of different genotype. Colitis was induced in mice with dextran sulphate sodium (DSS) and oxazolone (Oxa). Cytokine production was evaluated by mRNA quantification in colonic tissue and ELISA on supernatants of mesenteric lymph node cells.ResultsPrevalence of Hp2 was higher in CD and UC than in controls. In the confirmatory cohorts, Hp2 was over-transmitted to the affected offspring. Serum Hp concentrations were higher in individuals with genotypes Hp11 and Hp21 than in those with Hp22 (1.38 vs 0.89 g/l). DSS- and Oxa-induced colitis were more severe in Hp-deficient mice than in control mice and accompanied by higher concentrations (although not statistically significantly different) of tissue mRNA for cytokines. Interleukin-17 production was significantly higher in the presence of Hp-deficient serum compared with wild-type serum.ConclusionsThe Hp gene may play a role in susceptibility to inflammatory bowel disease. Its implication in other immune diseases underscores the common pathways between these diseases. Experimental models of colitis showed that Hp has a protective role in inflammatory colitis, most likely by inhibiting the production of Th1 and Th17 cytokines. [less ▲]

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See detailMolecular Reclassification of Crohn’s Disease by cluster analysis of genetic variants.
Cleynen, I.; Mahachie John, Jestinah ULg; Henckaerts, L. et al

in Gastroenterology (2010)

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See detailPolymorphisms in innate immunity genes predispose to bacteremia and death in the medical intensive care unit
Henckaerts, L.; Nielsen, K. R.; Steffensen, R. et al

in Critical Care Medicine (2009), 37(1), 192-2011-3

OBJECTIVE: Critically ill patients are at risk of sepsis, organ failure, and death. Studying the impact of genetic determinants may improve our understanding of the pathophysiology and allow ... [more ▼]

OBJECTIVE: Critically ill patients are at risk of sepsis, organ failure, and death. Studying the impact of genetic determinants may improve our understanding of the pathophysiology and allow identification of patients who would benefit from specific treatments. Our aim was to study the influence of single nucleotide polymorphisms in selected genes involved in innate immunity on the development of bacteremia or risk of death in patients admitted to a medical intensive care unit. DESIGN, SETTING, AND PATIENTS: DNA was available from 774 medical intensive care unit patients. We selected 31 single nucleotide polymorphisms in 14 genes involved in host innate immune defense. Serum levels of MASP2 and chemotactic capacity, phagocytosis, and killing capacity of monocytes at admission were quantified. Univariate Kaplan-Meier estimates with log-rank analysis and multivariate logistic regression were performed. Bootstrap resampling technique and ten-fold cross-validation were used to assess replication stability, prognostic importance of the variables, and repeatability of the final regression model. MAIN RESULTS: Patients with at least one NOD2 variant were shown to have a reduced phagocytosis by monocytes (p = 0.03) and a higher risk of bacteremia than wild-type patients (p = 0.02). The NOD2/TLR4 combination was associated with bacteremia using survival analyses (time to bacteremia development, log-rank p < 0.0001), univariate regression (p = 0.0003), and multivariate regression analysis (odds ratio [OR] 4.26, 95% confidence interval [CI] 1.85-9.81; p = 0.0006). Similarly, the same combination was associated with hospital mortality using survival analysis (log-rank p = 0.03), univariate regression (p = 0.02), and multivariate regression analysis (OR 2.27, 95% CI 1.09-4.74; p = 0.03). Also variants in the MASP2 gene were significantly associated with hospital mortality (survival analysis log-rank-p = 0.003; univariate regression p = 0.02; multivariate regression analysis OR 2.35, 95% CI 1.38-3.99; p = 0.002). CONCLUSIONS: Functional polymorphisms in genes involved in innate immunity predispose to severe infections and death, and may become part of a risk model, allowing identification of patients at risk, who could benefit from early introduction of specific preventive or therapeutic interventions. [less ▲]

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See detailDevelopment of psoriasiform skin lesions under anti-TNF therapy: a genetic link?
Cleynen, I.; Claes, B.; Nuytten, H. et al

in Conference Abstract Book (2008)

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See detailGenetic markers and the risk of complicated disease behaviour in Crohn's disease patients
Henckaerts, L.; Cleynen, I.; Joossens, M. et al

in Gastroenterology (2008), 134(4), 349-349

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See detailFaecal bacterial dgge profiles of Crohn's disease patients are different from those of their healthy first degree relatives and matched healthy controls
Joossens, M.; Vanhoutte, T.; De Preter, V. et al

in Gastroenterology (2007), 132(4), 704-704

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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 detailFaecal bacterial DGGE profiles of Crohn’s disease patients are different from those of their healthy first degree relatives and matched healthy controls
Joossens, M.; Vanhoutte, T.; De Preter, V. et al

in Acta Gastro-Enterologica Belgica (2007)

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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 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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