Mechanisms of disease: The human N-glycome

Biochim Biophys Acta. 2016 Aug;1860(8):1574-82. doi: 10.1016/j.bbagen.2015.10.016. Epub 2015 Oct 21.

Abstract

Background: The majority of human proteins are being modified by covalent attachment of complex oligosaccharides--glycans. Both glycans and polypeptide parts of a protein contribute to its structure and function, but contrary to polypeptide that is defined by the sequence of nucleotides in the corresponding gene, glycans are shaped by complex dynamic interactions between hundreds of enzymes, transcription factors, ion channels and other proteins.

Scope of review: An overview of current knowledge about the importance of N-glycans in normal human physiology and disease mechanisms, exemplified by IgG N-glycans.

Major conclusions: Recent technological development enabled systematic analysis of glycome composition in large epidemiological cohorts and clinical studies. However, the majority of these studies is still missing any glycomic component, and consequently also lacks this layer of biological information. Individual variation in glycosylation is potentially important for individualized disease risk, disease course and response to therapy. Evidence in support of this hypothesis is accumulating, but further studies are needed to enable understanding of the role of changes in protein glycosylation in disease.

General significance: Glycans are involved in virtually all physiological processes. Inter-individual variation in glycome composition is large, and these differences associate with disease risk, disease course and the response to therapy. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.

Keywords: Glycosylation in disease; Human glycome; IgG glycosylation; Protein glycosylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Genome, Human*
  • Humans
  • Metabolic Diseases* / genetics
  • Metabolic Diseases* / metabolism
  • Metabolic Diseases* / therapy
  • Polysaccharides* / genetics
  • Polysaccharides* / metabolism
  • Precision Medicine / methods*

Substances

  • Polysaccharides