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Human plasma glycome in attention-deficit hyperactivity disorder and autism spectrum disorders
Authors:Pivac Nela  Knezević Ana  Gornik Olga  Pucić Maja  Igl Wilmar  Peeters Hilde  Crepel An  Steyaert Jean  Novokmet Mislav  Redzić Irma  Nikolac Matea  Hercigonja Vesna Novković  Curković Katarina Dodig  Curković Mario  Nedić Gordana  Muck-Seler Dorotea  Borovecki Fran  Rudan Igor  Lauc Gordan
Affiliation:3. 3Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia,;4. 4University of Zagreb, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, 10000 Zagreb, Croatia,;5. 5Genos Ltd., Glycobiology Division, Planinska 1, 10000 Zagreb, Croatia,;6. 6Department of Genetics and Pathology, Rudbeck Laboratory; Uppsala University; Uppsala, Sweden,;12. 12Polyclinic Kocijan/Hercigonja, Lipovecka 17, 10000 Zagreb, Croatia,;8. 8Clinical Hospital Osijek, Department of Child and Adolescent Psychiatry, J. Huttlera 4, 31000 Osijek, Croatia,;9. 9Primary Care Unit Osijek, Park Kralja Petra Krešimira 4, 31000 Osijek, Croatia,;10. 10University of Zagreb Medical School, 10000 Zagreb, Croatia,
Abstract:Over a half of all proteins are glycosylated, and their proper glycosylation is essential for normal function. Unfortunately, because of structural complexity of nonlinear branched glycans and the absence of genetic template for their synthesis, the knowledge about glycans is lagging significantly behind the knowledge about proteins or DNA. Using a recently developed quantitative high throughput glycan analysis method we quantified components of the plasma N-glycome in 99 children with attention-deficit hyperactivity disorder (ADHD), 81 child and 5 adults with autism spectrum disorder, and a total of 340 matching healthy controls. No changes in plasma glycome were found to associate with autism spectrum disorder, but several highly significant associations were observed with ADHD. Further structural analysis of plasma glycans revealed that ADHD is associated with increased antennary fucosylation of biantennary glycans and decreased levels of some complex glycans with three or four antennas. The design of this study prevented any functional conclusions about the observed associations, but specific differences in glycosylation appears to be strongly associated with ADHD and warrants further studies in this direction.
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