Low level of the plasma sphingolipid, glucosylceramide, is associated with thrombotic diseases

• Type of Material: Article
• Authors: Hiroshi Deguchi, The Scripps Research Institute; Silvia Navarro, The Scripps Research Institute; Amanda B. Payne, Emory University; Darlene J. Elias, The Scripps Research Institute; Nicole F. Dowling, Emory University; Harland Austin, Emory University; Francisco España, La Fe Medical Research Institute; Pilar Medina, La Fe Medical Research Institute; W. Craig Hooper, Centers for Disease Control and Prevention; John H. Griffin, The Scripps Research Institute
• Language: English
• Date: 2017-07
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals, Inc on behalf of International Society on Thrombosis and Haemostasis.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/rth2.12018
• Title of Journal or Parent Work: Research and Practice in Thrombosis and Haemostasis
• ISSN: 2475-0379
• Volume: 1
• Issue: 1
• Start Page: 33
• End Page: 40
• Grant/Funding Information: Support was provided, in part, by grants HL021544, HL133728 and HL052246 from the National Institutes of Health and by Spanish grants PI12/00027, PI14/00079, and PI14/00512 from ISCIII and FEDER (Una manera de hacer Europa).
• Keywords: risk factor; myocardial infarction; epidemiology; venous thrombosis; glucosylceramide
• Research Categories: Health Sciences, Public Health; Health Sciences, Medicine and Surgery

Abstract

Essentials - Minor abundance plasma lipids, eg, glucosylceramide, can modulate blood coagulation reactions - This lipid was measured in plasmas of 1 myocardial infarction and 2 venous thrombosis populations - Low plasma glucosylceramide levels were found in each population compared to matched controls - Low plasma glucosylceramide levels are associated with venous and arterial thrombosis Background One previous pilot study suggested the association of low plasma glucosylceramide (GlcCer) levels with venous thrombosis (VTE) risk. Objective We aimed to confirm and evaluate the association of low plasma GlcCer levels with VTE and myocardial infarction (MI) occurrence, respectively. Patients and Methods We evaluated the association of GlcCer in two independent case‐control studies of Caucasian VTE populations (N=210 and 636) and one case‐control study of Caucasian MI patients (N=345). Result Plasma GlcCer levels in VTE patients were lower compared to controls in two independent VTE populations (5.0 vs 5.8 μg/mL, P=.003 for the Scripps registry, and 5.6 vs 6.0 μg/mL, P=.001 for the Valencia registry, respectively). A low plasma GlcCer level (below tenth percentile of controls) was associated with increased VTE occurrence (odds ratio [OR]=3.7 [95% CI, 1.8‐7.9] for Scripps registry and OR=2.1 [95% CI, 1.3‐3.3] for Valencia registry, respectively). For the MI study, the median GlcCer plasma level was lower in MI patients than in controls (4.3 vs 5.6 μg/mL, P<.001), and a low level of GlcCer (below tenth percentile of control) was associated with higher MI occurrence (OR=7.7, [95% CI, 4.3‐13.8]). Conclusion Lower concentration of GlcCer was associated with VTE occurrence in 2 independent studies and also with MI occurrence in 1 study.