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Thromb Haemost 2016; 116(03): 432-441
DOI: 10.1160/TH16-03-0178
Coagulation and Fibrinolysis
Schattauer GmbH

Identification of polymorphisms in Apolipoprotein M gene and their relationship with risk of recurrent venous thromboembolism

Abrar Ahmad
1   Center for Primary Health Care Research, Department of Clinical Sciences, Lund University/Skåne University Hospital, Malmö, Sweden
,
Kristina Sundquist
1   Center for Primary Health Care Research, Department of Clinical Sciences, Lund University/Skåne University Hospital, Malmö, Sweden
,
Bengt Zöller
1   Center for Primary Health Care Research, Department of Clinical Sciences, Lund University/Skåne University Hospital, Malmö, Sweden
,
Björn Dahlbäck
2   Department of Translational Medicine, Skåne University Hospital, Lund University, Sweden
,
Peter J. Svensson
3   Department of Coagulation Disorders, Skåne University Hospital, Lund University, Sweden
,
Jan Sundquist
1   Center for Primary Health Care Research, Department of Clinical Sciences, Lund University/Skåne University Hospital, Malmö, Sweden
,
Ashfaque A. Memon
1   Center for Primary Health Care Research, Department of Clinical Sciences, Lund University/Skåne University Hospital, Malmö, Sweden
› Author Affiliations Financial support: This work was supported by grants awarded to Dr Bengt Zöller by the Swedish Heart-Lung Foundation, ALF funding from Region Skåne awarded to Dr Bengt Zöller and Dr Kristina Sundquist, grants awarded to Dr Kristina Sundquist by the Swedish Research Council and grants awarded to Dr Jan Sundquist by King Gustaf V and Queen Victoria’s Foundation of Freemasons. The funders had no role in in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
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Publication History

Received: 03 March 2016

Accepted after major revision: 06 May 2016

Publication Date:
29 November 2017 (online)

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Summary

Apolipoprotein M (ApoM) plasma levels have been reported to be associated with risk of venous thromboembolism (VTE) recurrence. However, the role of genetic alterations in the ApoM gene in VTE recurrence remains unknown. The aim of this study was to identify genetic aberrations in ApoM gene in VTE recurrence and their role in prediction of VTE recurrence in a prospective follow-up study of 1465 VTE patients. During follow-up, 156 (10.6 %) patients had VTE recurrence. First screening of whole ApoM gene was performed by Sanger’s sequencing in selected age and sex matched non-recurrent and recurrent patients (n=95). In total six polymorphisms were identified and two polymorphisms (rs805297 and rs9404941) with minor allele frequency (MAF) ≥5 % were further genotyped in the whole cohort by Taqman PCR. ApoM rs805297 polymorphism was significantly associated with higher risk of VTE recurrence in males but not in females on both univariate (p= 0.038, hazard ratio = 1.72, confidence interval = 1.03–2.88) and on multivariate analysis adjusted with mild and severe thrombophilia, family history, location and acquired risk factors for VTE. However, ApoM rs9404941 polymorphism showed no significant association with risk of VTE recurrence in all patients as well as in different gender groups. Moreover, ApoM rs805297 and rs9404941 polymorphisms were not associated with the ApoM plasma levels. In conclusion, for the first time we have sequenced whole ApoM gene in VTE and identified six polymorphisms. ApoM rs805297 was significantly associated with higher risk of VTE recurrence in male but not in female patients.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Apolipoprotein M - recurrent VTE - multivariate analysis

 

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