Most inflammatory bowel diseases (IBDs) are classic complex disorders represented by common alleles. Here we aimed to define the genetic architecture of pediatric and adult-onset IBDs for the Polish population. A total of 1495 patients were recruited, including 761 patients with Crohn’s disease (CD; 424 pediatric), 734 patients with ulcerative colitis (UC; 390 pediatric), and 934 healthy controls. Allelotyping employed a pooled-DNA genome-wide association study (GWAS) and was validated by individual genotyping. Whole exome sequencing (WES) was performed on 44 IBD patients diagnosed before 6 years of age, 45 patients diagnosed after 40 years of age, and 18 healthy controls. Altogether, out of 88 selected SNPs, 31 SNPs were replicated for association with IBD. A novel BRD2 (rs1049526) association reached significance of P = 5.2 × 10−11 and odds ratio (OR) = 2.43. Twenty SNPs were shared between pediatric and adult patients; 1 and 7 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare and potentially deleterious variants in IBD-associated or innate immunity-associated genes. Deleterious alleles in both groups were over-represented among rare variants in affected children. Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare and deleterious variants in affected children suggests a contribution by yet unexplained genetic components.
Objectives. The enhanced activity of matrix endopeptidases (MMPs) involved in the degradation of connective tissue has been noted in tissue samples from the digestive tract in inflammatory bowel disease (IBD), however sera concentrations of MMPs, a potential tool for diagnostic tests in IBD patients, have not been established so far. The goal of the studies was to evaluate the concentrations of MMP-3 and MMP-9, in the sera of children suffering from ulcerative colitis (UC) in relation to disease activity. Material and Methods. The study was comprised of 31 children with UC (aged 3-18 years) and 37 children in the control group (aged 1-18 years). Disease activity was estimated using the Truelove-Witts scale. MMP-3 and -9 concentrations were determined using ELISA tests. Results. Median MMP-3 concentrations were 18.4 ng/mL (95% CI: 12.5-24.3) for moderate and severe, 4.35 ng/mL (95% CI: 2.5-7.8) for the mild form of UC and 1.8 ng/mL (95% CI: 1.2-2.5) for the control group. Median MMP-9 concentrations were 18.0 ng/mL (95% CI: 2.83-36.6) for moderate and severe, 1.55 ng/mL (95% CI: 0.4-3.0) for the mild form of UC and 1.3 ng/mL (95% CI: 0.7-1.96) for the control group. Serum MMP-3 and MMP-9 concentrations in the moderate group were higher than those in the mild and control groups (p < 0.001). MMP-3 concentrations in the mild group also differed from those in the control group (p < 0.001). Among the parameters studied (MMP-3, MMP-9, CRP and ESR), MMP-3 had the highest discriminative value (AUC = 0.9, p < 0.001, sensitivity = 71%, specificity = 92%) in distinguishing patients with UC from healthy individuals. Conclusions. Elevation of MMP-3 and MMP-9 concentrations along with the disease activity suggests the possibility of their application in the evaluation of the clinical activity of UC (Adv Clin Exp Med 2014, 23, 1, 103-110).
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