Molecular prediction of disease risk and severity in a large Dutch Crohn's disease cohort

Item does not contain fulltextBACKGROUND: Crohn's disease and ulcerative colitis have a complex genetic background. We assessed the risk for both the development and severity of the disease by combining information from genetic variants associated with inflammatory bowel disease (IBD). METHODS: We studied 2804 patients (1684 with Crohn's disease and 1120 with ulcerative colitis) and 1350 controls from seven university hospitals. Details of the phenotype were available for 1600 patients with Crohn's disease and for 800 with ulcerative colitis. Genetic association for disease susceptibility was tested for the nucleotide-binding and oligomerisation domain 2 gene (NOD2), the IBD5 locus, the Drosophila discs large homologue 5 and autophagy-related 16-like 1 genes (DLG5 and ATG16L1) and the interleukin 23 receptor gene (IL23R). Interaction analysis was performed for Crohn's disease using the most associated single nucleotide polymorphism (SNP) for each locus. Odds ratios were calculated in an ordinal regression analysis with the number of risk alleles as an independent variable to analyse disease development and severity. RESULTS: Association with Crohn's disease was confirmed for NOD2, IBD5, DLG5, ATG16L1 and IL23R. Patients with Crohn's disease carry more risk alleles than controls (p = 3.85 x 10(-22)). Individuals carrying an increasing number of risk alleles have an increasing risk for Crohn's disease, consistent with an independent effects multiplicative model (trend analysis p = 4.25 x 10(-23)). Patients with Crohn's disease with a more severe disease course, operations or an age of onset below 40 years have more risk alleles compared to non-stricturing, non-penetrating behaviour (p = 0.0008), no operations (p = 0.02) or age of onset above 40 years (p = 0.028). CONCLUSION: Crohn's disease is a multigenic disorder. An increase in the number of risk alleles is associated with an increased risk for the development of Crohn's disease and with a more severe disease course. Combining information from the known common risk polymorphisms may enable clinicians to predict the course of Crohn's disease

Het klinische spectrum van de ziekte van Pompe.

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Endothermy and chorusing behaviour in the African platypleurine cicada Pycna semiclara (Germar, 1834) (Hemiptera: Cicadidae)

Cicadas use acoustic signals to find mates and therefore offer a phylogenetically independent opportunity to test the generality of ideas about acoustic communication that were developed from studies of other animals. Pycna semiclara (Germar, 1834) (Hemiptera: Cicadidae) is a forest-dwelling platypleurine cicada that uses its calling song to form choruses and attract mates. Additionally, P. semiclara produces an encounter call that is involved in courtship and also in spacing males within choruses. Males generally call from exposed trunks and branches within the understory but clear of the undergrowth and fight with other males that call within about 50 cm of them. Choruses sing sporadically throughout the day but focus most of their calling activity into half-hour bouts at dawn and dusk. Body size and ambient temperature had no significant effect on spectral or temporal characteristics of the calling song. Body temperature measurements indicate that P. semiclara thermoregulates endothermically, with a body temperature of more than 22 °C above ambient temperature being measured during calling activity at dusk. Such endothermy provides an advantage to the cicadas by allowing them to call during crepuscular hours when atmospheric conditions are most optimal for acoustic communication and predation risks are minimal. Coincidentally, endogenously regulating body temperature allows the temporal characteristics of the call to be unaffected by ambient temperature changes