Association of recurrent venous thromboembolism and circulating microRNAs.


Journal

Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977

Informations de publication

Date de publication:
13 02 2019
Historique:
received: 06 07 2018
accepted: 04 02 2019
entrez: 15 2 2019
pubmed: 15 2 2019
medline: 21 8 2019
Statut: epublish

Résumé

Patients with unprovoked first venous thromboembolism (VTE) are at a high risk of recurrence. Although circulating microRNAs (miRNAs) have been found to be associated with VTE and are markers of hypercoagulability, this study is the first to examine whether circulating miRNAs are associated with the risk of VTE recurrence. A nested case-control study design was used where plasma samples were obtained from 78 patients with unprovoked VTE from the Malmö Thrombophilia Study (MATS). A total of 39 VTE patients with recurrent VTE (cases) were matched with 39 VTE patients without recurrent VTE (controls) defined by age and sex (MATS population). Plasma levels of 179 different miRNAs were evaluated in the 78 samples (after anticoagulant treatment was stopped) using qPCR. A total of 110 miRNAs were detected in all samples. Among those, 12 miRNAs (miR-15b-5p, miR-106a-5p, miR-197-3p, miR-652-3p, miR-361-5p, miR-222-3p, miR-26b-5p, miR-532-5p, miR-27b-3p, miR-21-5p, miR-103a-3p, and miR-30c-5p) were found to be associated with recurrent VTE after multiple correction test and conditional logistic regression analysis. A further analysis showed that miR-15b-5p, miR-197-3p, miR-27b-3p, and miR-30c-5p exhibited a trend over time, with a larger difference in miRNA levels between cases and controls for earlier recurrence. Of these 12 miRNAs, 8 miRNAs significantly correlated with circulating transforming growth factor β1/2 (TGFβ1/2). Three of them correlated with platelet count. We have identified 12 plasma miRNAs that may have the potential to serve as novel, non-invasive predictive biomarkers for VTE recurrence.

Sections du résumé

BACKGROUND
Patients with unprovoked first venous thromboembolism (VTE) are at a high risk of recurrence. Although circulating microRNAs (miRNAs) have been found to be associated with VTE and are markers of hypercoagulability, this study is the first to examine whether circulating miRNAs are associated with the risk of VTE recurrence.
RESULTS
A nested case-control study design was used where plasma samples were obtained from 78 patients with unprovoked VTE from the Malmö Thrombophilia Study (MATS). A total of 39 VTE patients with recurrent VTE (cases) were matched with 39 VTE patients without recurrent VTE (controls) defined by age and sex (MATS population). Plasma levels of 179 different miRNAs were evaluated in the 78 samples (after anticoagulant treatment was stopped) using qPCR. A total of 110 miRNAs were detected in all samples. Among those, 12 miRNAs (miR-15b-5p, miR-106a-5p, miR-197-3p, miR-652-3p, miR-361-5p, miR-222-3p, miR-26b-5p, miR-532-5p, miR-27b-3p, miR-21-5p, miR-103a-3p, and miR-30c-5p) were found to be associated with recurrent VTE after multiple correction test and conditional logistic regression analysis. A further analysis showed that miR-15b-5p, miR-197-3p, miR-27b-3p, and miR-30c-5p exhibited a trend over time, with a larger difference in miRNA levels between cases and controls for earlier recurrence. Of these 12 miRNAs, 8 miRNAs significantly correlated with circulating transforming growth factor β1/2 (TGFβ1/2). Three of them correlated with platelet count.
CONCLUSION
We have identified 12 plasma miRNAs that may have the potential to serve as novel, non-invasive predictive biomarkers for VTE recurrence.

Identifiants

pubmed: 30760335
doi: 10.1186/s13148-019-0627-z
pii: 10.1186/s13148-019-0627-z
pmc: PMC6374897
doi:

Substances chimiques

Circulating MicroRNA 0
TGFB1 protein, human 0
TGFB2 protein, human 0
Transforming Growth Factor beta1 0
Transforming Growth Factor beta2 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Pagination

28

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Auteurs

Xiao Wang (X)

Center for Primary Health Care Research, Wallenberglaboratoriet, Lund University/Region Skåne, Inga-Marie Nilssons gata 53, plan 6, Box 50332, 202 13, Malmö, Sweden. xiao.wang@med.lu.se.

Kristina Sundquist (K)

Center for Primary Health Care Research, Wallenberglaboratoriet, Lund University/Region Skåne, Inga-Marie Nilssons gata 53, plan 6, Box 50332, 202 13, Malmö, Sweden.
Department of Family Medicine and Community Health, Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai, New York, USA.
Center for Community-based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Matsue, Japan.

Peter J Svensson (PJ)

Department of Coagulation Disorders, Lund University, Malmö, University Hospital, Malmö, Sweden.

Hamideh Rastkhani (H)

Center for Primary Health Care Research, Wallenberglaboratoriet, Lund University/Region Skåne, Inga-Marie Nilssons gata 53, plan 6, Box 50332, 202 13, Malmö, Sweden.

Karolina Palmér (K)

Center for Primary Health Care Research, Wallenberglaboratoriet, Lund University/Region Skåne, Inga-Marie Nilssons gata 53, plan 6, Box 50332, 202 13, Malmö, Sweden.

Ashfaque A Memon (AA)

Center for Primary Health Care Research, Wallenberglaboratoriet, Lund University/Region Skåne, Inga-Marie Nilssons gata 53, plan 6, Box 50332, 202 13, Malmö, Sweden.

Jan Sundquist (J)

Center for Primary Health Care Research, Wallenberglaboratoriet, Lund University/Region Skåne, Inga-Marie Nilssons gata 53, plan 6, Box 50332, 202 13, Malmö, Sweden.
Department of Family Medicine and Community Health, Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai, New York, USA.
Center for Community-based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Matsue, Japan.

Bengt Zöller (B)

Center for Primary Health Care Research, Wallenberglaboratoriet, Lund University/Region Skåne, Inga-Marie Nilssons gata 53, plan 6, Box 50332, 202 13, Malmö, Sweden.

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