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Alpha 2-macroglobulin 5 bp insertion/deletion polymorphism increases the risk of recurrent venous thromboembolism

Ahmad, Abrar LU ; Sundquist, Kristina LU ; Svensson, Peter J. LU ; Sundquist, Jan LU ; Zöller, Bengt LU and Memon, Ashfaque A. LU (2018) In Gene Reports 13. p.104-109
Abstract

Alpha 2-macroglobulin (A2M) is a protease inhibitor that has been reported to neutralize thrombin, which may decrease the risk of thrombosis. A 5-base pairs (bp) insertion/deletion polymorphism (rs3832852) at the splice acceptor site of exon 18 has been shown to affect the binding of A2M with proteases. However, the role of this important variant in A2M in recurrent VTE is unknown. We investigated the role of 5 bp insertion/deletion polymorphism in VTE recurrence in a follow up study. A2M 5 bp insertion/deletion polymorphism was genotyped in Malmö Thrombophilia Study (MATS, n = 1465, with follow up of ~10 years) by TaqMan Allelic Discrimination assay. Univariate Cox regression analysis showed that A2M polymorphism was significantly... (More)

Alpha 2-macroglobulin (A2M) is a protease inhibitor that has been reported to neutralize thrombin, which may decrease the risk of thrombosis. A 5-base pairs (bp) insertion/deletion polymorphism (rs3832852) at the splice acceptor site of exon 18 has been shown to affect the binding of A2M with proteases. However, the role of this important variant in A2M in recurrent VTE is unknown. We investigated the role of 5 bp insertion/deletion polymorphism in VTE recurrence in a follow up study. A2M 5 bp insertion/deletion polymorphism was genotyped in Malmö Thrombophilia Study (MATS, n = 1465, with follow up of ~10 years) by TaqMan Allelic Discrimination assay. Univariate Cox regression analysis showed that A2M polymorphism was significantly associated with higher risk of VTE recurrence (hazard ratio [HR] = 2.61, 95% confidence interval [CI] = 1.06–6.45, P = 0.037). This association remained significant (HR = 2.61, 95% CI = 1.06–6.47, P = 0.038) even after adjusting for sex, family history of VTE, thrombophilia and acquired risk factors for VTE. In conclusion, our results indicate that patients with A2M 5 bp insertion/deletion polymorphism are at significantly higher risk of VTE recurrence and this may predict VTE recurrence.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cox regression analysis, Splice site, Venous thromboembolism
in
Gene Reports
volume
13
pages
6 pages
publisher
Elsevier
external identifiers
  • scopus:85053381535
ISSN
2452-0144
DOI
10.1016/j.genrep.2018.09.007
language
English
LU publication?
yes
id
cf428009-5474-48eb-a277-70fa4108038d
date added to LUP
2018-10-08 11:12:22
date last changed
2019-02-20 11:29:52
@article{cf428009-5474-48eb-a277-70fa4108038d,
  abstract     = {<p>Alpha 2-macroglobulin (A2M) is a protease inhibitor that has been reported to neutralize thrombin, which may decrease the risk of thrombosis. A 5-base pairs (bp) insertion/deletion polymorphism (rs3832852) at the splice acceptor site of exon 18 has been shown to affect the binding of A2M with proteases. However, the role of this important variant in A2M in recurrent VTE is unknown. We investigated the role of 5 bp insertion/deletion polymorphism in VTE recurrence in a follow up study. A2M 5 bp insertion/deletion polymorphism was genotyped in Malmö Thrombophilia Study (MATS, n = 1465, with follow up of ~10 years) by TaqMan Allelic Discrimination assay. Univariate Cox regression analysis showed that A2M polymorphism was significantly associated with higher risk of VTE recurrence (hazard ratio [HR] = 2.61, 95% confidence interval [CI] = 1.06–6.45, P = 0.037). This association remained significant (HR = 2.61, 95% CI = 1.06–6.47, P = 0.038) even after adjusting for sex, family history of VTE, thrombophilia and acquired risk factors for VTE. In conclusion, our results indicate that patients with A2M 5 bp insertion/deletion polymorphism are at significantly higher risk of VTE recurrence and this may predict VTE recurrence.</p>},
  author       = {Ahmad, Abrar and Sundquist, Kristina and Svensson, Peter J. and Sundquist, Jan and Zöller, Bengt and Memon, Ashfaque A.},
  issn         = {2452-0144},
  keyword      = {Cox regression analysis,Splice site,Venous thromboembolism},
  language     = {eng},
  month        = {12},
  pages        = {104--109},
  publisher    = {Elsevier},
  series       = {Gene Reports},
  title        = {Alpha 2-macroglobulin 5 bp insertion/deletion polymorphism increases the risk of recurrent venous thromboembolism},
  url          = {http://dx.doi.org/10.1016/j.genrep.2018.09.007},
  volume       = {13},
  year         = {2018},
}