GlycA: A Composite Nuclear Magnetic Resonance Biomarker of Systemic Inflammation

Otvos, James D.; Shalaurova, Irina; Wolak-Dinsmore, Justyna; Connelly, Margery A.; Mackey, Rachel H.; Stein, James H.; Tracy, Russell P.

doi:10.1373/clinchem.2014.232918

Cited by 319 publications

(502 citation statements)

References 37 publications

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“…The association of ␣ 1 acid glycoprotein with mortality was slightly attenuated when hsCRP was added into the model. These results for ␣ 1 acid glycoprotein, which is a major contributor to our quantified GlycA biomarker, are congruent with our study (9 ).…”

Section: Discussionsupporting

confidence: 92%

“…The GlycA NMR signal is chemically nonspecific in origin, coming from the N-acetyl methyl groups of GlcNAc residues on the antennary branches of serum glycoproteins (9 ). GlycA concentrations are due in aggregate primarily to contributions from ␣ 1 acid glycoprotein, haptoglobin, ␣ 1 antitrypsin, ␣ 1 antichemotrypsin, and transferrin.…”

Section: Discussionmentioning

confidence: 99%

“…The NMR measurement of GlycA, its chemical origins, and its analytic and biological variability have been described in detail (9 ). NMR spectra used for GlycA analysis were those acquired for NMR LipoProfile testing at the CLIA-certified LipoScience (now LabCorp) clinical laboratory in Raleigh, NC (8 ).…”

Section: Lipids Lipoprotein Particles and Other Laboratory Assaysmentioning

confidence: 99%

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Comparison of the Predictive Value of GlycA and Other Biomarkers of Inflammation for Total Death, Incident Cardiovascular Events, Noncardiovascular and Noncancer Inflammatory-Related Events, and Total Cancer Events

et al. 2016

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BACKGROUND GlycA is a biomarker that reflects integrated concentrations and glycosylation states of several acute-phase proteins. We studied the association of GlycA and inflammatory biomarkers with future death and disease. METHODS A total of 6523 men and women in the Multi-Ethnic Study of Atherosclerosis who were free of overt cardiovascular disease (CVD) and in generally good health had a baseline blood sample taken. We assayed high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer. A spectral deconvolution algorithm was used to quantify GlycA signal amplitudes from automated nuclear magnetic resonance (NMR) LipoProfile® test spectra. Median follow-up was 12.1 years. Among 4 primary outcomes, CVD events were adjudicated, death was by death certificate, and chronic inflammatory-related severe hospitalization and death (ChrIRD) and total cancer were classified using International Classification of Diseases (ICD) codes. We used Poisson regression to study baseline GlycA, hsCRP, IL-6, and d-dimer in relation to total death, CVD, ChrIRD, and total cancer. RESULTS Relative risk per SD of GlycA, IL-6, and d-dimer for total death (n = 915); for total CVD (n = 922); and for ChrIRD (n = 1324) ranged from 1.05 to 1.20, independently of covariates. In contrast, prediction from hsCRP was statistically explained by adjustment for other inflammatory variables. Only GlycA was predictive for total cancer (n = 663). Women had 7% higher values of all inflammatory biomarkers than men and had a significantly lower GlycA prediction coefficient than men in predicting total cancer. CONCLUSIONS The composite biomarker GlycA derived from NMR is associated with risk for total death, CVD, ChrIRD, and total cancer after adjustment for hsCRP, IL-6, and d-dimer. IL-6 and d-dimer contribute information independently of GlycA.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Lipids Lipoprotein Particles and Other Laboratory Assaysmentioning

confidence: 99%

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Comparison of the Predictive Value of GlycA and Other Biomarkers of Inflammation for Total Death, Incident Cardiovascular Events, Noncardiovascular and Noncancer Inflammatory-Related Events, and Total Cancer Events

et al. 2016

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“…Additional support for this hypothesis comes from recent studies of an NMR biomarker, GlycA. GlycA is a signal that mostly arises from N-acetylglucosamine residues attached to the plasma proteins and it has been shown to correlate with a wide spectrum of inflammatory diseases, including incident type 2 diabetes [22,23]. Higher branching of N-glycans, which we found in our study, also implies a higher number of N-acetylglucosamine residues in glycans attached to the plasma proteins (similar to higher GlyA signal).…”

Section: Discussionmentioning

confidence: 98%

Increased plasma N-glycome complexity is associated with higher risk of type 2 diabetes

et al. 2017

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Aims/hypothesis Better understanding of type 2 diabetes and its prevention is a pressing need. Changes in human plasma Nglycome are associated with many diseases and represent promising diagnostic and prognostic biomarkers. Variations in glucose metabolism directly affect glycosylation through the hexosamine pathway but studies of plasma glycome in type 2 diabetes are scarce. The aim of this study was to determine whether plasma protein N-glycome is changed in individuals who are at greater risk of developing type 2 diabetes. Methods Using a chromatographic approach, we analysed Nlinked glycans from plasma proteins in two populations comprising individuals with registered hyperglycaemia during critical illness (increased risk for development of type 2 diabetes) and individuals who stayed normoglycaemic during the same condition: AcuteInflammation (59 cases (ORCADES and SABRE populations) all presented with increased branching, galactosylation and sialylation of plasma protein N-glycans and these changes were of similar magnitude. Conclusions/interpretation Increased complexity of plasma N-glycan structures is associated with higher risk of developing type 2 diabetes and poorer regulation of blood glucose levels. Although further research is needed, this finding could offer a potential new approach for improvement in prevention of diabetes and its complications.

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“…The work of Otvos et al in this issue of Clinical Chemistry (2 ) adds to the accumulating evidence that automated quantitative analytics provided by modern NMR platforms is a powerful tool to reveal potential new biomarkers for disease risk assessment and clinical applications. The authors applied advanced spectral analysis and presented quantification of a composite NMR resonance reflecting glycoprotein acetylation, termed GlycA.…”

mentioning

confidence: 99%

Serum Nuclear Magnetic Resonance Spectroscopy: One More Step toward Clinical Utility

Ala‐Korpela

2015

Clinical Chemistry

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GlycA: A Composite Nuclear Magnetic Resonance Biomarker of Systemic Inflammation

Cited by 319 publications

References 37 publications

Comparison of the Predictive Value of GlycA and Other Biomarkers of Inflammation for Total Death, Incident Cardiovascular Events, Noncardiovascular and Noncancer Inflammatory-Related Events, and Total Cancer Events

Comparison of the Predictive Value of GlycA and Other Biomarkers of Inflammation for Total Death, Incident Cardiovascular Events, Noncardiovascular and Noncancer Inflammatory-Related Events, and Total Cancer Events

Increased plasma N-glycome complexity is associated with higher risk of type 2 diabetes

Serum Nuclear Magnetic Resonance Spectroscopy: One More Step toward Clinical Utility

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