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

Ahmad, Abrar LU ; Sundquist, Kristina LU ; Zöller, Bengt LU ; Dahlbäck, Björn LU ; Svensson, Peter J LU ; Sundquist, Jan LU and Memon, Ashfaque A LU (2016) In Thrombosis and Haemostasis 116(3). p.41-432
Abstract

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)... (More)

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.

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author
organization
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type
Contribution to journal
publication status
published
subject
in
Thrombosis and Haemostasis
volume
116
issue
3
pages
10 pages
publisher
F K Schattauer Verlag Gmbh
ISSN
0340-6245
DOI
10.1160/TH16-03-0178
language
English
LU publication?
yes
id
c922404d-e3a7-4894-bf16-3dfd3f72c605
date added to LUP
2016-09-09 08:15:34
date last changed
2016-10-28 16:18:43
@misc{c922404d-e3a7-4894-bf16-3dfd3f72c605,
  abstract     = {<p>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.</p>},
  author       = {Ahmad, Abrar and Sundquist, Kristina and Zöller, Bengt and Dahlbäck, Björn and Svensson, Peter J and Sundquist, Jan and Memon, Ashfaque A},
  issn         = {0340-6245},
  language     = {eng},
  month        = {08},
  number       = {3},
  pages        = {41--432},
  publisher    = {ARRAY(0xb01b6c8)},
  series       = {Thrombosis and Haemostasis},
  title        = {Identification of polymorphisms in Apolipoprotein M gene and their relationship with risk of recurrent venous thromboembolism},
  url          = {http://dx.doi.org/10.1160/TH16-03-0178},
  volume       = {116},
  year         = {2016},
}