Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2020; 26(32): 4866-4877
Published online Aug 28, 2020. doi: 10.3748/wjg.v26.i32.4866
Inactive matrix Gla protein is elevated in patients with inflammatory bowel disease
Darko Brnic, Dinko Martinovic, Piero Marin Zivkovic, Daria Tokic, Marino Vilovic, Doris Rusic, Ivana Tadin Hadjina, Christian Libers, Sandro Glumac, Daniela Supe-Domic, Ante Tonkic, Josko Bozic
Darko Brnic, Piero Marin Zivkovic, Ivana Tadin Hadjina, Department of Gastroenterology, University Hospital of Split, Split 21000, Croatia
Dinko Martinovic, Daria Tokic, Department of Emergency Medicine, Institute of Emergency Medicine of Split-Dalmatia County, Split 21000, Croatia
Marino Vilovic, Christian Libers, Josko Bozic, Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
Doris Rusic, Department of Pharmacy, University of Split School of Medicine, Split 21000, Croatia
Sandro Glumac, Department of Anesthesiology and Intensive Care, University Hospital of Split, Split 21000, Croatia
Daniela Supe-Domic, Department of Medical Laboratory Diagnostics, University Hospital of Split, Split 21000, Croatia
Ante Tonkic, Department of Internal Medicine, University of Split School of Medicine, Split 21000, Croatia
Author contributions: Brnic D, Martinovic D and Bozic J were involved in the study conceptualization, methodology design, funding acquisition and manuscript drafting and writing; Zivkovic PM, Tokic D, Vilovic M, Tadin H and Libers C were involved in the literature investigation, software statistical analysis and manuscript visualization and editing; Supe-Domic D, Rusic D and Glumac S were involved in patient sampling, laboratory analysis and manuscript editing; Tonkic A was involved in supervision and project administration.
Institutional review board statement: The study was reviewed and approved by the University Hospital of Split Institutional Review Board (Approval No. 2181-147-01/06/M.S.-17-2).
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: Data set is available from the corresponding author at email: josko.bozic@mefst.hr.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Josko Bozic, MD, PhD, Associate Professor, Department of Pathophysiology, University of Split School of Medicine, Soltanska 2, Split 21000, Croatia. josko.bozic@mefst.hr
Received: May 30, 2020
Peer-review started: May 30, 2020
First decision: June 12, 2020
Revised: July 30, 2020
Accepted: August 15, 2020
Article in press: August 15, 2020
Published online: August 28, 2020
Processing time: 89 Days and 16.9 Hours
Abstract
BACKGROUND

Matrix Gla protein (MGP) is a vitamin K dependent peptide which has an established role in suppression of vascular calcification. Recent studies have pointed to a possible link between immunomodulatory effect of MGP and inflammatory bowel disease (IBD).

AIM

To compare plasma levels of dephosphorylated and uncarboxylated MGP (dp-ucMGP) between IBD patients and controls.

METHODS

This cross-sectional study was conducted on 70 patients with IBD (30 patients with ulcerative colitis and 40 patients with Crohn’s disease) and 60 age and gender matching healthy controls. Plasma dp-ucMGP levels were analyzed from blood samples by CLIA method using IDS-iSYS InaKtif MGP (Immunodiagnostic Systems, Frankfurt, Germany) according to the manufacturer's instructions. fecal calprotectin (FC) levels were determined from stool samples by turbidimetric immunoassay method using Bühlmann fecal calprotectin turbo assay (Bühlmann Laboratories Aktiengesellschaft, Schonenbuch, Switzerland). Other parameters were analyzed according to the standard laboratory procedures.

RESULTS

Plasma levels of dp-ucMGP were significantly higher in patients with IBD compared to the healthy control group (629.83 ± 124.20 pmol/mL vs 546.7 ± 122.09 pmol/mL, P < 0.001), and there was no significant difference between patients with Crohn’s disease and patients with ulcerative colitis (640.02 ± 131.88 pmol/mL vs 616.23 ± 113.92 pmol/mL, P = 0.432). Furthermore, a significant positive correlation of plasma dp-ucMGP levels was found with both FC levels (r = 0.396, P < 0.001) and high sensitivity C-reactive protein (hsCRP) levels (r = 0.477, P < 0.001). Moreover, in the total study population a significant positive correlation was found between dp-ucMGP with age (r = 0.210, P = 0.016) and waist circumference (r = 0.264, P = 0.002). Multiple linear regression analysis showed that dp-ucMGP levels retained significant association with FC (β ± SE, 0.06 ± 0.02, P = 0.003).

CONCLUSION

Study results support experimental data of MGP immunomodulatory IBD effect and indicate potential involvement in the pathophysiology of the disease, and possibly extraintestinal manifestations.

Keywords: Matrix Gla protein; Inflammatory bowel disease; Fecal calprotectin; Ulcerative colitis; Crohn's disease

Core tip: Matrix Gla protein (MGP) is well-established as a protector against vascular calcification. Recent studies pointed to a possible link between MGP and inflammatory bowel disease (IBD). Our study found significantly higher inactive plasma MGP levels in patients with IBD compared to the healthy controls and there were no differences between patients with ulcerative colitis and Crohn’s disease. Furthermore, there was a significant positive correlation between inactive plasma MGP levels with both fecal calprotectin and high sensitivity C-reactive protein levels. These results imply that MGP is somehow involved in complex IBD pathophysiology.