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Lactose intolerance with adult-onset is due to the inadequate enzymatic activity of lactasephlorizin hydrolase (LPH). It is frequently seen in patients with Crohn disease, but the mechanism remains to be elucidated. Two DNA genotypes, C/C(-13910) and G/G(-22018), located upstream from the LCT locus, the gene encoding for LPH, were recently identified as representing genetic markers for lactose intolerance. We utilized these two DNA genotypes to study their role in inflammatory bowel disease.We investigated the prevalence of these two DNA variants using specific restriction enzyme digest assays in 166 patients with Crohn disease, in 120 healthy first-degree relatives of Crohn disease patients, in 63 patients with ulcerative colitis and in 187 healthy individuals.The analysis revealed a frequency of 21.4% of the 2 genotypes for adult-type hypolactasia in our studied German cohort of healthy individuals, which is higher than previously reported (15%) based on the hydrogen (H2) breath test. This might indicate a higher sensitivity of genotyping, but it has to be confirmed in larger cohorts. No significant difference was detectable in the frequency of the C/C(-13910) and G/G(-22018) genotypes in patients with Crohn disease (C/C(-13910): 21.7%; G/G(-22018): 22.3%) compared to first-degree relatives (C/C(-13910): 21.7%; G/G(-22018): 20.8%), patients with ulcerative colitis (C/C(-13910): 20.3%; G/G(-22018): 20.3%) and healthy individuals (C/C(-13910): 21.4%; G/G(-22018): 21.4%).The C/C(-13910) and G/G(-22018) genotype of adult-type hypolactasia is not associated with susceptibility to the pathogenesis of Crohn disease and ulcerative colitis.

Genetic predisposition has been suggested to play an important role in the pathogenesis of inflammatory bowel diseases (IBDs). Linkage studies have identified a Crohn's disease susceptibility locus on chromosome 14 (14q11-12; IBD4). Interleukin-25 (IL-25) is a newly identified proinflammatory cytokine that has been shown to promote Th2 responses by inducing cytokines such as IL-4, IL-5 and IL-13. The IL-25 gene is located within this susceptibility region at 14q11.2. As IBDs are characterized by an imbalance of the Th1/Th2 cytokine response, we hypothesized that genetic alterations within the IL-25 gene might contribute to IBD. First, direct sequencing of the coding regions of the IL-25 gene in 40 patients with Crohn's disease or ulcerative colitis revealed only a newly reported polymorphism (c424C/A) in exon 2. Next, the frequency of this polymorphism was further investigated in 151 patients with Crohn's disease, 111 patients with ulcerative colitis, and 119 healthy controls to determine its clinical relevance. The genotypes of the c424C/A polymorphism did not reveal any significant differences between patients with Crohn's disease or ulcerative colitis and controls. Genoytype-phenotype relations in patients with Crohn's disease showed a comparable distribution of the c424C/A polymorphism in all subgroups of the Vienna classification. In summary, our data indicate that genetic alterations in the coding regions of the IL-25 gene are unlikely to play a role in IBDs, but the c424C/A polymorphism in the IL-25 gene should be investigated for a potential association with other chronic inflammatory and inherited disorders such as autoimmune diseases.

The therapeutic success of low doses of glucocorticoids is mediated entirely by classical genomic effects, whereas that of high doses is also mediated to an as yet unknown extent by nongenomic effects. We assessed the relative therapeutic importance of these nongenomic effects in pulse therapy.A [3H]dexamethasone radioligand binding assay was used to measure the number of glucocorticoid receptor sites (R, given as number of sites per cell) and glucocorticoid receptor binding affinity (Kd, given in nM) in peripheral blood mononuclear cells isolated from 26 healthy control blood donors and 27 patients with rheumatic diseases. Patients were divided into 4 groups on the basis of their glucocorticoid dose: 0 mg (Group A),or = 0.25 mg (Group B), 0.25 to 1 mg (Group C), and1 mg (Group D) of prednisolone equivalent per kg per day.Sex independent normal values of 3605 +/- 1136 for R and 5.39 +/- 3.4 for Kd were found. At 5407 +/- 1968, the number of receptor sites in patients not receiving glucocorticoid therapy (Group A) was significantly higher than that of controls (p0.01). In patients receiving glucocorticoid therapy this value was reduced at 3855 +/- 866 (Group B), 3358 +/- 963 (Group C), and 2685 +/- 962 (Group D). The values in Groups C and D were significantly lower than those in untreated patients (p0.02).In pulse therapy doses of glucocorticoids that exceed receptor saturation are administered for several days, but in addition significant receptor downregulation occurs. Therefore, we assume an increase in the relative contribution of the nongenomic effects of glucocorticoids to the therapeutic success under these conditions.