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The genetics of venous thromboembolism: a systematic review of thrombophilia families

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Abstract

Genetic risk factors are important for the occurrence and prognosis of venous thromboembolism (VTE). The studies of thrombophilia families are important for dissecting the genetic background of the thrombotic disease. We conducted the systematic review of all published family-based studies on VTE genetics across all racial groups through PubMed and Embase prior to 13th April 2020. This systematic review of 287 families (including 225 Caucasian families, 52 East Asian families, and families of other ethnicities) revealed a total of 21 different genes; the five most reported mutated genes were F5 (88/287, 30.7%), SERPINC1 (67/287, 23.3%), PROC (65/287, 22.6%), F2 (40/287, 13.9%) and PROS1 (48/287, 16.7%). For Caucasian families, F5 mutations were most frequently reported at 37.8% (85/225), while PROS1 mutations were most frequently reported, at 40.4% (21/52), for East Asian families (Chinese, Japanese and Korean). Factor V Leiden was reported more frequently in Caucasians than in East Asians. Missense mutations were reported frequently in the SERPINC1, PROC and PROS1 genes. In conclusion, our study found the most likely mutated genes associated with VTE among different ethnic groups and provided indications for VTE genetic testing and research in the future.

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Abbreviations

APCR:

Activated protein C resistance

AT:

Antithrombin

DVT:

Deep venous thrombosis

FVL:

Factor V Leiden

GWAS:

Genome wide association study

PAI-1:

Plasminogen activator inhibitor-1

PC:

Protein C

PCR:

Polymerase chain reaction

PS:

Protein S

PTE:

Pulmonary thromboembolism

SNPs:

Single nucleotide polymorphisms

VTE:

Venous thromboembolism

WES:

Whole exome sequencing

IIa:

Activated FactorII

Va:

Activated FactorV

VIIa:

Activated FactorVII

Xa:

Activated FactorX

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Funding

This work was supported by the Fund of The National Key Research and Development Program of China (No. 2016YFC0905600), the Fundamental Research Funds for the Central Universities (NO. 3332018184), CAMS Innovation Fund for Medical Sciences (CIFMS) (2018-I2M-1-003).

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Author notes

  1. Dr. Yu Zhang and Zhu Zhang contribute equally to this study.

Authors and Affiliations

  1. China-Japan Friendship Hospital, Capital Medical University, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China

    Yu Zhang, Zhenguo Zhai & Chen Wang

  2. Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China

    Yu Zhang, Zhu Zhang, Shi Shu, Wanmu Xie, Jun Wan, Zhenguo Zhai & Chen Wang

  3. Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China

    Yu Zhang, Zhu Zhang, Shi Shu, Wanmu Xie, Jun Wan, Zhenguo Zhai & Chen Wang

  4. National Clinical Research Center for Respiratory Diseases, NO 2, East Yinghua Road, Chaoyang District, Beijing, 100029, China

    Yu Zhang, Zhu Zhang, Shi Shu, Wanmu Xie, Jun Wan, Zhenguo Zhai & Chen Wang

  5. Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Zhu Zhang, Zhenguo Zhai & Chen Wang

  6. Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China

    Wenquan Niu

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  1. Yu Zhang
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  2. Zhu Zhang
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  3. Shi Shu
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  6. Jun Wan
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  8. Chen Wang
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Contributions

CW and ZZ conceived and designed the study, having full access to all of the data in the study and taking responsibility for the content of the manuscript. YZ, ZZ and SS analyzed the data, took responsibility for the accuracy of the data analysis and wrote the first draft of the manuscript. WN, WJ and WX contributed to the interpretation of the data and clinical inputs. All authors were involved in the revision of the manuscript for important intellectual content and approved the final version to be published.

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Correspondence to Zhenguo Zhai or Chen Wang.

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Zhang, Y., Zhang, Z., Shu, S. et al. The genetics of venous thromboembolism: a systematic review of thrombophilia families. J Thromb Thrombolysis 51, 359–369 (2021). https://doi.org/10.1007/s11239-020-02203-7

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