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Semin Thromb Hemost 2021; 47(06): 662-668
DOI: 10.1055/s-0040-1722271
Review Article

The Association between Blood-Based Global DNA Methylation and Venous Thromboembolism

Xiao Wang 
1   Center for Primary Health Care Research, Lund University, Malmö, Sweden
,
Ashfaque A. Memon
1   Center for Primary Health Care Research, Lund University, Malmö, Sweden
,
Karolina Palmér
1   Center for Primary Health Care Research, Lund University, Malmö, Sweden
,
Peter J. Svensson
2   Department of Coagulation Disorders, Lund University Hospital, Malmö, Sweden
,
Jan Sundquist
1   Center for Primary Health Care Research, Lund University, Malmö, Sweden
3   Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York
4   Department of Functional Pathology, Center for Community-based Healthcare Research and Education (CoHRE), School of Medicine, Shimane University, Izumo, Japan
,
Kristina Sundquist
1   Center for Primary Health Care Research, Lund University, Malmö, Sweden
3   Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York
4   Department of Functional Pathology, Center for Community-based Healthcare Research and Education (CoHRE), School of Medicine, Shimane University, Izumo, Japan
› Author Affiliations Funding This work was supported by grants awarded to Kristina Sundquist by the Swedish Heart-Lung Foundation, ALF funding from Region Skåne awarded to Jan Sundquist and Kristina Sundquist, and grants awarded to Kristina Sundquist and Jan Sundquist by the Swedish Research Council.
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Abstract

Alterations in DNA methylation patterns have been associated with many diseases. However, the role of DNA methylation in venous thromboembolism (VTE) is not well established. The aim of this study was to investigate a possible association between global DNA methylation and VTE. The study participants consisted of 168 individuals including 74 patients with primary VTE from the Malmö Thrombophilia Study (MATS) and 94 healthy controls. Among 74 primary VTE patients, 37 suffered VTE recurrence during the follow-up period; 37 nonrecurrent VTE patients were included for comparison. Blood-based global DNA methylation was assessed by an enzyme-linked immunosorbent assay. Global DNA methylation was significantly higher in primary VTE patients compared with the healthy controls (median: 0.17 vs. 0.08%; p < 0.001). After stratification of data from primary VTE patients according to sex, the association between higher global DNA methylation and shorter recurrence-free survival time was of borderline statistical significance in males (β = –0.2; p = 0.052) but not in females (β = 0.02; p = 0.90). Our results show that global DNA methylation is associated with primary VTE and that higher levels of global DNA methylation may be associated with early VTE recurrence in males but not in females. Further investigation on the role of DNA methylation as a diagnostic or preventive biomarker in VTE is warranted.

Keywords

venous thromboembolism - DNA methylation - recurrent venous thromboembolism

Note

The datasets used and/or analyzed during the study are available from the corresponding author on reasonable request.


Ethical Approval

All the patients provided written consent according to the Declaration of Helsinki before enrollment in the study. The study was approved by the Ethics Committee of Lund University (LU 237/2007).


Authors' Contributions

X.W., A.A.M., K.P., P.S., J.S., and K.S. conceived and designed the study. P. S. collected the samples and clinical data. X.W. and A.A.M. designed the experiments and selected the samples. X. W. performed the experiments. X.W., K.P., J.S. and K.S. analyzed the data and contributed to the interpretation of the results. X.W., K.P., and A.A.M. wrote the manuscript. All authors provided critical feedback and approved the final manuscript.




Publication History

Article published online:
30 December 2020

© 2020. Thieme. All rights reserved.

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