Glycome as Biomarkers

Shinohara, Yasuro; Furukawa, Yoshihiro; Miura, Yoshiaki

doi:10.1007/978-94-007-7696-8_23

Cited by 8 publications

(2 citation statements)

References 72 publications

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“…Beyond that, aberrant glycosylation is involved in key pathological steps of tumor development and is even considered a new hallmark of cancer (15)(16)(17). Glycans are considered as potential therapeutic targets (18) and biomarkers for early diagnosis and disease prognosis (19)(20)(21)(22), which makes glycobiology a promising field for future clinical applications. An example of glycoprotein biomarker is AFP-L3-the fucosylated fraction of alpha-fetoprotein-that was approved by the U.S. Food and Drug Administration as a diagnostic marker of primary hepatocellular carcinoma (21).…”

Section: Introductionmentioning

confidence: 99%

Defining the genetic control of human blood plasma N-glycome using genome-wide association study

Sharapov

Tsepilov

Klarić

et al. 2019

Human Molecular Genetics

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Glycosylation is a common post-translational modification of proteins. Glycosylation is associated with a number of human diseases. Defining genetic factors altering glycosylation may provide a basis for novel approaches to diagnostic and pharmaceutical applications. Here we report a genome-wide association study of the human blood plasma N-glycome composition in up to 3811 people measured by Ultra Performance Liquid Chromatography (UPLC) technology. Starting with the 36 original traits measured by UPLC, we computed an additional 77 derived traits leading to a total of 113 glycan traits. We studied associations between these traits and genetic polymorphisms located on human autosomes. We discovered and replicated 12 loci. This allowed us to demonstrate an overlap in genetic control between total plasma protein and IgG glycosylation. The majority of revealed loci contained genes that encode enzymes directly involved in glycosylation (FUT3/FUT6, FUT8, B3GAT1, ST6GAL1, B4GALT1, ST3GAL4, MGAT3 and MGAT5) and a known regulator of plasma protein fucosylation (HNF1A). However, we also found loci that could possibly ref lect other more complex aspects of glycosylation process. Functional genomic annotation suggested the role of several genes including DERL3, CHCHD10, TMEM121, IGH and IKZF1. The hypotheses we generated may serve as a starting point for further functional studies in this research area.

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Section: Introductionmentioning

confidence: 99%

Defining the genetic control of human blood plasma N-glycome using genome-wide association study

Sharapov

Tsepilov

Klarić

et al. 2019

Human Molecular Genetics

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“…Adequate glycosylation is required for the normal physiological action of glycoproteins, while aberrant glycosylation is increasingly implicated in human diseases [7][8][9] . Glycans are considered to be potential therapeutic targets [10][11][12] , essential part of therapeutics [13][14][15] , as well as biomarkers [16][17][18] , which makes glycobiology a promising field for future clinical applications. N-glycosylation is the most abundant type of glycosylation 1 and, unlike other types, is specific to a consensus asparagine-containing sequence (Asn-X-Ser/Thr, where X is any amino acid except Pro) in the protein's primary structure.…”

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confidence: 99%

A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins

Sharapov,

Timoshchuk,

Zaytseva

et al. 2024

Preprint

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More than a half of plasma proteins are N-glycosylated. Most of them are synthesized, glycosylated, and secreted to the bloodstream by liver and lymphoid tissues. While associations with N-glycosylation are implicated in the rising number of liver, cardiometabolic, and immune diseases, little is known about the genetic regulation of this process. Here, we performed the largest genome-wide association study of N-glycosylation of the blood plasma proteome in 10,000 individuals. We doubled the number of genetic loci known to be associated with blood N-glycosylation by identifying 16 novel loci and prioritizing 13 novel genes contributing to N-glycosylation. Among these were theGCKR,TRIB1,HP, SERPINA1andCFHgenes. These genes are predominantly expressed in the liver and show a previously unknown genetic link between plasma protein N-glycosylation, metabolic and liver diseases, and inflammatory response. By integrating glycomics, proteomics, transcriptomics, and genomics, we provide a resource that facilitates deeper exploration of disease pathogenesis and supports the discovery of glycan-based biomarkers.

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Quantitative analysis of total serum glycome in human and mouse

et al. 2016

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Model mice are frequently used in drug discovery research. Knowledge of similarities and differences between the mouse and human glycomes is critical when model mice are used for the discovery of glycan-related biomarkers and targets for therapeutic intervention. Since few comparative glycomic studies between human and mouse have been conducted, we performed a comprehensive comparison of the major classes of glycans in human and mouse sera using mass spectrometric and liquid chromatographic analyses. Up to 131 serum glycans, including N-glycans, free oligosaccharides (fOSs), glycosaminoglycans, O-glycans, and glycosphingolipid (GSL)-glycans, were quantified. In both serum samples, N-glycans were the most abundant in the total serum glycome, while fOSs were the least abundant. As expected, the diversity of sialic acid (i.e. Neu5Ac vs. Neu5Gc) was the major species difference between human and mouse in terms of N- and O-glycosylation, while GSL-glycomic profiles were completely different, even when the sialic acid diversity was taken into consideration. Furthermore, total serum glycomics of STAM mouse were unveiled as an initial step to identify novel biomarkers of liver diseases, with which we could identify several glycans with expression significantly increased or decreased expression.

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Glycome as Biomarkers

Cited by 8 publications

References 72 publications

Defining the genetic control of human blood plasma N-glycome using genome-wide association study

Defining the genetic control of human blood plasma N-glycome using genome-wide association study

A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins

Quantitative analysis of total serum glycome in human and mouse

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