  Familial Aggregation and Antimicrobial Response Dose-Dependently Affect the Risk for Crohn's Disease; Van Steen, Kristel  ; et alin Inflammatory Bowel Diseases (2010), 16(1), 58-67 Background: An increased risk of Crohn's disease (CD) has been reported consistently in first-degree relatives of patients. Our aim was to test whether a combination of CD-associated genes involved in ... [more ▼] Background: An increased risk of Crohn's disease (CD) has been reported consistently in first-degree relatives of patients. Our aim was to test whether a combination of CD-associated genes involved in innate immunity and/or antibody responses to microbial antigens may be valuable in identifying healthy relatives at risk. Methods: We investigated 86 families from Beloium and northern France, 45 with at least 3 first-degree relatives with CD, 24 with a single case, and 17 control families without inflammatory bowel disease (IBD). The cohort consisted of 186 CD patients, 290 healthy relatives, and 142 controls (total 618). Genetic (NOD2, NODI, TLR4, CARD8) and serologic markers (ASCA, ACMA, ALCA, ACCA, A Sigma MA, OmpC, CBir1, I2) were determined in all subjects. All Belgian families were prospectively followed up for 54 months. Results: In multiple-affected families, an increment of affected first-degree relatives and of positive antibodies were additive risks factors for CD (P < 0.0001), independent of NOD2 mutations. When comparing subjects from multiple-affected families, having 3 additional first-degree relatives with CD and 1 additional positive antibody increased the odds for CD to 9.19 (95% confidence interval [CI]: 4.07-20.80). After a follow-up of 54 months among all Belgian families, a total of 4 new diagnoses of IBD were confirmed in the multiple-affected families only, resulting in a 57-fold increase in incidence within multiple-affected families compared to the known incidence of IBD in our region. Conclusions: We found an additive risk increment for CD in subjects from multicase families per additional affected relative and per additional positive antibody, independent of NOD2. Furthermore, a very high disease incidence was observed in these multiple-affected families. [less ▲] Detailed reference viewed: 14 (2 ULg)Mucosal gene signatures to predict response to infliximab in patients with inflammatory bowel disease; ; Van Steen, Kristel et alin Acta Gastro-Enterologica Belgica (2008) Detailed reference viewed: 20 (14 ULg)Stability Of Gut Microbiota Over Time In Crohn's Disease Patients Compared To Healthy Relatives; ; Van Steen, Kristel et alin Journal of Crohn’s and Colitis [=JCC] (2008), 2(1), 94 Detailed reference viewed: 15 (9 ULg)Long-term efficacy of infliximab and colectomy-free survival in outpatients with refractory ulcerative colitis.; ; et al in Journal of Crohn’s and Colitis [=JCC] (2008), 2(1), 3 Detailed reference viewed: 29 (13 ULg)Stability of gut microbiota over time in Crohn's disease patients compared to healthy relatives; ; Van Steen, Kristel et alin Gastroenterology (2008), 134(4), 653-653 Detailed reference viewed: 12 (8 ULg)Mucosal gene signatures to predict response to infliximab in patients with inflammatory bowel disease; ; Van Steen, Kristel et alin Journal of Crohn’s and Colitis [=JCC] (2008), 2(1), 64 Detailed reference viewed: 3 (2 ULg)Genetic markers and the risk of complicated disease behaviour in Crohn's disease patients; ; et al in Gastroenterology (2008), 134(4), 349-349 Detailed reference viewed: 7 (4 ULg)Mucosal gene signatures to predict response to infliximab in patients with inflammatory bowel disease.; ; Van Steen, Kristel et alin Gastroenterology (2008), 134 Detailed reference viewed: 11 (11 ULg)Microarray study of mucosal antimicrobial peptides in patients with inflammatory bowel disease before and after infliximab treatment.; ; Van Steen, Kristel et alin Journal of Crohn’s and Colitis [=JCC] (2008), 2(1), 60 Detailed reference viewed: 13 (6 ULg)Long term stability of gut microbiota in Crohn’s disease patients compared to healthy relatives; ; Van Steen, Kristel et alin Acta Gastro-Enterologica Belgica (2008), 71 Detailed reference viewed: 8 (2 ULg)Faecal bacterial dgge profiles of Crohn's disease patients are different from those of their healthy first degree relatives and matched healthy controls; ; et al in Gastroenterology (2007), 132(4), 704-704 Detailed reference viewed: 11 (3 ULg)Mixed IBD families: A distinct entity within IBD; Van Steen, Kristel ; et alin Gastroenterology (2007), 132(4), 450-450 Detailed reference viewed: 7 (4 ULg)Faecal bacterial DGGE profiles of Crohn’s disease patients are different from those of their healthy first degree relatives and matched healthy controls; ; et al in Acta Gastro-Enterologica Belgica (2007) Detailed reference viewed: 10 (5 ULg)New serological markers in inflammatory bowel disease are associated with complicated disease behavior; ; 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 ▲] Detailed reference viewed: 15 (5 ULg)Faecal bacterial molecular profiles of Crohn’s disease patients differ from their healthy relatives and matched healthy controls.; ; et al in Gut (2007), 56(Suppl III), 5 Detailed reference viewed: 6 (4 ULg) |
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