Endothelial cell protein C receptor gene 6936A/G polymorphism is associated with venous thromboembolism

Yin,Guancheng; Jin,Xing; Ming,Hanxin; Zheng,Xiao; Zhang,Deqing

doi:10.3892/etm.2012.510

June 2012 Volume 3 Issue 6

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June 2012 Volume 3 Issue 6

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Article

Endothelial cell protein C receptor gene 6936A/G polymorphism is associated with venous thromboembolism

Authors:
- Guancheng Yin
- Xing Jin
- Hanxin Ming
- Xiao Zheng
- Deqing Zhang
View Affiliations / Copyright

Affiliations: Department of Vascular Surgery, Shandong Provincial Hospital, Shandong University, Jinan 250012, P.R. China, Department of General Surgery, Taian Central Hospital, Taian 271000, P.R. China, Department of Laboratory, Taian Central Hospital, Taian 271000, P.R. China
Pages: 989-992
|
Published online on: March 12, 2012

https://doi.org/10.3892/etm.2012.510
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Abstract

Venous thromboembolism (VTE) is a common, yet complex disorder. Genetic factors have been suggested to play a role in disease development. We, therefore, conducted a case-control study to examine the potential association of the 6936A/G polymorphism in the endothelial cell protein C receptor (EPCR) gene with the occurrence of venous thromboembolism. We measured the plasma levels of soluble EPCR (sEPCR) in blood samples collected from 112 patients with VTE and 112 age- and gender-matched healthy donors using enzyme-linked immunosorbent assay (ELISA) and amplified the EPCR gene product by PCR. Gene product bands were sequenced to identify EPCR gene polymorphisms. We found that the 6936 AG and GG genotypes were over-represented in the VTE patients. By multivariate analysis, subjects carrying the 6936 G allele were found to have an increased risk of thrombosis (OR=1.784; 95% CI, 1.113-2.891; P<0.05). In conclusion, the EPCR gene 6936A/G polymorphism, which is associated with elevated plasma sEPCR levels, is a potential candidate risk factor for venous thromboembolism.

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1.	Davies KA, Ireland H, Athanassiou P, Loizou S, Lane D and Walport MJ: Factor V Leiden mutation and venous thrombosis. Lancet. 345:132–133. 1995. View Article : Google Scholar : PubMed/NCBI
2.	Laposata M: The prothrombin G20210A mutation: a new high-prevalence congenital risk factor for thrombosis. Gastroenterology. 116:213–215. 1999. View Article : Google Scholar : PubMed/NCBI
3.	Seligsohn U and Lubetsky A: Genetic susceptibility to venous thrombosis. N Engl J Med. 344:1222–1231. 2001. View Article : Google Scholar : PubMed/NCBI
4.	Frosst P, Blom HJ, Milos R, et al: A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 10:111–113. 1995. View Article : Google Scholar : PubMed/NCBI
5.	Stearns-Kurosawa DJ, Kurosawa S, Mollica JS, Ferrell GL and Esmon CT: The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc Natl Acad Sci USA. 93:10212–10216. 1996. View Article : Google Scholar : PubMed/NCBI
6.	Centelles MN, Puy C, López-Sagaseta J, Fukudome K, Montes R and Hermida J: Blocking endothelial protein C receptor (EPCR) accelerates thrombus development in vivo. Thromb Haemost. 103:1239–1244. 2010. View Article : Google Scholar : PubMed/NCBI
7.	Ridker PM: Inherited risk factors for venous thromboembolism: implications for clinical practice. Clin Cornerstone. 4:18–30. 2002. View Article : Google Scholar : PubMed/NCBI
8.	Koster T, Rosendaal FR, Briët E, et al: Protein C deficiency in a controlled series of unselected outpatients: an infrequent but clear risk factor for venous thrombosis (Leiden Thrombophilia Study). Blood. 85:2756–2761. 1995.
9.	Fukudome K and Esmon CT: Identification, cloning and regulation of a novel endothelial cell protein C/activated protein C receptor. J Biol Chem. 269:26486–26491. 1994.PubMed/NCBI
10.	Gu JM, Katsuura Y, Ferrell GL, Grammas P and Esmon CT: Endotoxin and thrombin elevate rodent endothelial cell protein C receptor mRNA levels and increase receptor shedding in vivo. Blood. 95:1687–1693. 2000.PubMed/NCBI
11.	Kurosawa S, Stearns-Kurosawa DJ, Carson CW, D'Angelo A, Della Valle P and Esmon CT: Plasma levels of endothelial cell protein C receptor are elevated in patients with sepsis and systemic lupus erythematosus: lack of correlation with thrombomodulin suggests involvement of different pathological processes. Blood. 91:725–727. 1998.
12.	Espana F, Vaya A, Mira Y, et al: Low level of circulating activated protein C is a risk factor for venous thromboembolism. Thromb Haemost. 86:1368–1373. 2001.PubMed/NCBI
13.	Navarro S, Medina P, Mira Y, et al: Haplotypes of the EPCR gene, prothrombin levels, and the risk of venous thrombosis in carriers of the prothrombin G20210A mutation. Haematologica. 93:885–891. 2008. View Article : Google Scholar : PubMed/NCBI
14.	Zöller B: Familial thrombophilia: clinical and molecular analysis of Swedish families with inherited resistance to activated protein C or protein S deficiency. Scand J Clin Lab Invest Suppl. 226:19–46. 1996.PubMed/NCBI
15.	Villoutreix BO, Blom AM and Dahlbäck B: Structural prediction and analysis of endothelial cell protein C/activated protein C receptor. Protein Eng. 12:833–840. 1999. View Article : Google Scholar : PubMed/NCBI
16.	Saposnik B, Reny JL, Gausem P, Emmerich J, Aiach M and Gandrille S: A haplotype of the EPCR gene is associated with increased plasma levels of sEPCR and is a candidate risk factor for thrombosis. Blood. 103:1311–1318. 2004. View Article : Google Scholar : PubMed/NCBI
17.	Yamagishi K, Cushman M, Heckbert SR, Tsai MY and Folsom AR: Lack of association of soluble endothelial protein C receptor and PROCR 6936A/G polymorphism with the risk of venous thromboembolism in a prospective study. Br J Haematol. 145:221–226. 2009. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Endothelial cell protein C receptor gene 6936A/G polymorphism is associated with venous thromboembolism

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