OBJECTIVES: Inflammatory bowel disease (IBD) is today a global disease, the incidence of which is growing in the pediatric population. This prospective study aims to decipher IBD incidence and its trend in a pediatric population through 16 years in the South Moravian Region of the Czech Republic. METHODS: We evaluated data concerning 358 pediatric patients with newly diagnosed IBD at University Hospital Brno, which is a gastroenterology center for the entire pediatric population (0-18 years) and cares for all pediatric IBD patients in the South Moravian Region (1,187,667 inhabitants). RESULTS: The study encompassed 3,488,907 children during 16 years. We diagnosed 192 children (53.6%) with Crohn disease (CD), 123 (34.4%) with ulcerative colitis (UC), and 43 (12.0%) with IBD-unclassified (IBD-U). The incidence of IBD increased from 3.8 (CD 2.9, UC 0.9, and IBD-U 0.0) per 100 000/year in 2002 to 14.7 (CD 9.8, UC 4.0, and IBD-U 0.9) per 100,000/year in 2017 (P < 0.001). The overall IBD incidence per 100,000/year was 9.8 (95% confidence interval [CI]: 8.8--10.9). Constituent incidences per 100,000/year were CD 5.2 (95% CI: 4.5--6.0), UC 3.4 (95% CI: 2.8--4.0), and IBD-U 1.2 (95% CI: 0.9--1.6). IBD incidence was projected to reach 18.9 per 100,000/year in 2022. CONCLUSIONS: The overall incidence of pediatric IBD in the Czech Republic is increasing, and especially that of CD, whereas trends in UC and IBD-U appear to be constant. These data highlight the need to identify risk factors involved in the rising incidence of IBD.
- MeSH
- dítě MeSH
- idiopatické střevní záněty * epidemiologie MeSH
- incidence MeSH
- lidé MeSH
- prospektivní studie MeSH
- ulcerózní kolitida * epidemiologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
The enzyme UDP-N-acetylglucosamine: α-d-mannoside β-1-6 N-acetylglucosaminyltransferase V (GnT-V) catalyzes the transfer of GlcNAc from the UDP-GlcNAc donor to the α-1-6-linked mannose of the trimannosyl core structure of glycoproteins to produce the β-1-6-linked branching of N-linked oligosaccharides. β-1-6-GlcNAc-branched N-glycans are associated with cancer growth and metastasis. Therefore, the inhibition of GnT-V represents a key target for anti-cancer drug development. However, the development of potent and specific inhibitors of GnT-V is hampered by the lack of information on the three-dimensional structure of the enzyme and on the binding characteristics of its substrates. Here we present the first 3D structure of GnT-V as a result of homology modeling. Various alignment methods, docking the donor and acceptor substrates, and molecular dynamics simulation were used to construct seven homology models of GnT-V and characterize the binding of its substrates. The best homology model is consistent with available experimental data. The three-dimensional model, the structure of the enzyme catalytic site and binding information obtained for the donor and acceptor can be useful in studies of the catalytic mechanism and design of inhibitors of GnT-V.
- Klíčová slova
- GlcNAc-TV, N-glycosylation, glycosyltransferase, homology model, molecular dynamics,
- MeSH
- glykosyltransferasy chemie MeSH
- lidé MeSH
- mannosa chemie MeSH
- molekulární konformace * MeSH
- molekulární modely MeSH
- N-acetylglukosaminyltransferasy chemie MeSH
- polysacharidy chemie genetika MeSH
- simulace molekulární dynamiky MeSH
- substrátová specifita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase MeSH Prohlížeč
- glykosyltransferasy MeSH
- mannosa MeSH
- N-acetylglukosaminyltransferasy MeSH
- polysacharidy MeSH
