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

Author:
  • Abrar Ahmad
  • Kristina Sundquist
  • Bengt Zöller
  • Björn Dahlbäck
  • Peter J Svensson
  • Jan Sundquist
  • Ashfaque A Memon
Publishing year: 2016-08-30
Language: English
Pages: 41-432
Publication/Series: Thrombosis and Haemostasis
Volume: 116
Issue: 3
Document type: Journal article
Publisher: F K Schattauer Verlag Gmbh

Abstract english

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.

Keywords

  • Medical Genetics

Other

Published
  • Family Medicine, Psychiatric Epidemiology and Migration
  • Family Medicine, Cardiovascular Epidemiology and Lifestyle
  • Clinical Coagulation, Malmö
  • ISSN: 0340-6245
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E-mail: abrar [dot] ahmad [at] med [dot] lu [dot] se

Assistant researcher

Diabetic Complications

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Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00