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Polymorphisms in PARK2 and MRPL37 are associated with higher risk of recurrent venous thromboembolism in a sex-specific manner

Sundquist, Kristina LU ; Ahmad, Abrar LU ; Svensson, Peter J. LU ; Zöller, Bengt LU ; Sundquist, Jan LU and Memon, Ashfaque A. LU (2018) In Journal of Thrombosis and Thrombolysis 46(2). p.154-165
Abstract

Recent studies indicate that mitochondrial DNA (mtDNA) dysfunction is a biomarker of oxidative stress and can predict the risk of cardiovascular diseases (CVDs). Genetic variants in PARK2 (rs4708928) and MRPL37 (rs10888838) genes have been shown to be associated with altered levels of mtDNA in a sex-specific manner. However, the role of these genetic variants in risk assessment of recurrent venous thromboembolism (VTE) is unknown. We investigated the role of these polymorphisms in VTE recurrence in patients from the Malmö thrombophilia study (MATS, n = 1465), followed for ~ 10 years. Genotyping was performed by TaqMan polymerase chain reaction. Female patients with PARK2 polymorphism had significantly higher risk of VTE recurrence... (More)

Recent studies indicate that mitochondrial DNA (mtDNA) dysfunction is a biomarker of oxidative stress and can predict the risk of cardiovascular diseases (CVDs). Genetic variants in PARK2 (rs4708928) and MRPL37 (rs10888838) genes have been shown to be associated with altered levels of mtDNA in a sex-specific manner. However, the role of these genetic variants in risk assessment of recurrent venous thromboembolism (VTE) is unknown. We investigated the role of these polymorphisms in VTE recurrence in patients from the Malmö thrombophilia study (MATS, n = 1465), followed for ~ 10 years. Genotyping was performed by TaqMan polymerase chain reaction. Female patients with PARK2 polymorphism had significantly higher risk of VTE recurrence (Hazard ratio [HR] = 2.39, 95% confidence interval [CI] 1.09–5.24) and male patients with MRPL37 polymorphism had a significantly higher risk of VTE recurrence (HR = 1.79, 95% CI 1.01–3.17) on multivariate Cox regression analysis. Combined analysis of these polymorphism with factor V Leiden (FVL) showed that female patients with both, FVL and PARK2 polymorphism had even higher risk of VTE recurrence (HR = 4.49, 95% CI 1.58–12.75) compared to FVL or PARK2 polymorphism alone or both wild-type (reference). Similarly, male patients with both FVL and MRPL37 polymorphism had significantly higher risk of VTE recurrence (HR = 2.97, 95% CI 1.45–6.08) compared to those with FVL or MRPL37 polymorphisms alone or the reference group. Polymorphisms in nuclear genome regulating mtDNA together with FVL may be promising biomarkers for predicting VTE recurrence in a sex specific manner. The abstract should be followed by 3-4 bullet points that highlight the major findings. The final bullet point should address future research.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Factor V Leiden, Genetic risk factor, Mitochondria, Predictive biomarkers, Recurrent VTE
in
Journal of Thrombosis and Thrombolysis
volume
46
issue
2
pages
154 - 165
publisher
Springer
external identifiers
  • scopus:85045630643
ISSN
0929-5305
DOI
10.1007/s11239-018-1662-x
language
English
LU publication?
yes
id
0d8b3beb-2824-4efe-a7fe-6a634a3ecd6d
date added to LUP
2018-05-02 15:18:04
date last changed
2019-03-19 03:53:55
@article{0d8b3beb-2824-4efe-a7fe-6a634a3ecd6d,
  abstract     = {<p>Recent studies indicate that mitochondrial DNA (mtDNA) dysfunction is a biomarker of oxidative stress and can predict the risk of cardiovascular diseases (CVDs). Genetic variants in PARK2 (rs4708928) and MRPL37 (rs10888838) genes have been shown to be associated with altered levels of mtDNA in a sex-specific manner. However, the role of these genetic variants in risk assessment of recurrent venous thromboembolism (VTE) is unknown. We investigated the role of these polymorphisms in VTE recurrence in patients from the Malmö thrombophilia study (MATS, n = 1465), followed for ~ 10 years. Genotyping was performed by TaqMan polymerase chain reaction. Female patients with PARK2 polymorphism had significantly higher risk of VTE recurrence (Hazard ratio [HR] = 2.39, 95% confidence interval [CI] 1.09–5.24) and male patients with MRPL37 polymorphism had a significantly higher risk of VTE recurrence (HR = 1.79, 95% CI 1.01–3.17) on multivariate Cox regression analysis. Combined analysis of these polymorphism with factor V Leiden (FVL) showed that female patients with both, FVL and PARK2 polymorphism had even higher risk of VTE recurrence (HR = 4.49, 95% CI 1.58–12.75) compared to FVL or PARK2 polymorphism alone or both wild-type (reference). Similarly, male patients with both FVL and MRPL37 polymorphism had significantly higher risk of VTE recurrence (HR = 2.97, 95% CI 1.45–6.08) compared to those with FVL or MRPL37 polymorphisms alone or the reference group. Polymorphisms in nuclear genome regulating mtDNA together with FVL may be promising biomarkers for predicting VTE recurrence in a sex specific manner. The abstract should be followed by 3-4 bullet points that highlight the major findings. The final bullet point should address future research.</p>},
  author       = {Sundquist, Kristina and Ahmad, Abrar and Svensson, Peter J. and Zöller, Bengt and Sundquist, Jan and Memon, Ashfaque A.},
  issn         = {0929-5305},
  keyword      = {Factor V Leiden,Genetic risk factor,Mitochondria,Predictive biomarkers,Recurrent VTE},
  language     = {eng},
  number       = {2},
  pages        = {154--165},
  publisher    = {Springer},
  series       = {Journal of Thrombosis and Thrombolysis},
  title        = {Polymorphisms in PARK2 and MRPL37 are associated with higher risk of recurrent venous thromboembolism in a sex-specific manner},
  url          = {http://dx.doi.org/10.1007/s11239-018-1662-x},
  volume       = {46},
  year         = {2018},
}