Background: Deep venous thrombosis (DVT) can lead to a serious fatal
pulmonary embolism. Many genetic risk factors may predispose to DVT; one of
these is the mutation in the PROCR gene responsible for the production
of endothelial protein C receptor (EPCR), which plays an important role in
activation of protein C (PC). The objective of the present study was to examine
the association between the rs867186 and rs9574 polymorphism in the PROCR gene and the occurrence of DVT in Sudanese individuals. Methods: A total of 100
Sudanese DVT patients and 100 apparently healthy individuals were recruited for
this study. Ethylene diamine tetraacetic acie (EDTA)-anti- coagulated blood
samples were collected from all participants. Genomic DNA was extracted and PROCR gene product was amplified by a standard ploymerase chain reaction (PCR)
reaction. PCR products were sequenced to identify PROCR gene
polymorphisms. Results: The frequency of mutated allele of rs867186 was
significantly higher in the DVT patient (41%) than in healthy control (21%).
The presence of mutated allele of rs867486 increases the risk of DVT 3 folds.
There was no significant difference in the frequency of mutated allele of
rs9574 polymorphism between the DVT patients and the healthy control subjects.
Further, it does not show an increase in the risk of DVT. The adjustment of
gender, ethnic group, and body mass index (BMI) does not change the significance
of each single nucleotide polymorphism (SNP) as a risk factor for DVT. Conclusion:
It can be concluded that Sudanese individuals carrying the mutated allele
rs867186 polymorphism were at risk to develop DVT, while the mutated allele of
rs9574 polymorphism is not a risk factor for DVT in Sudanese individuals.
Cite this paper
Abuagla, H. A. , Ahmed, A. O. , Bolad, A. K. and Adam, K. M. (2016). Relation between Endothelial Protein C Receptor Gene Polymorphisms rs867186 and rs9574, and the Risk of Deep Vein Thrombosis in Sudanese. Open Access Library Journal, 3, e2310. doi: http://dx.doi.org/10.4236/oalib.1102310.
Kesieme, E., Kesieme, C., Jebbin, N., Irekpita, E.
and Dongo, A. (2011) Deep Vein Thrombosis: A Clinical Review. Journal of Blood Medicine, 2, 59-69. http://dx.doi.org/10.2147/JBM.S19009
Fukudome, K. and Esmon, C.T. (1994) Identification,
Cloning, and Regulation of a Novel Endothelial Cell Protein C/ Activated
Protein C Receptor. Journal
of Biological Chemistry, 269, 26486-26491.
Kurosawa, S., Stearns-Kurosawa, D.J., Hidari, N.
and Esmon, C.T. (1997) Identification of Functional Endothelial Protein
C Receptor in Human Plasma. Journal of
Clinical Investigation, 100, 411-418. http://dx.doi.org/10.1172/JCI119548
Saposnik, B.,
Reny, J.L.,
Gaussem, P.,
Emmerich, J.,
Aiach, M. and Gandrille, S. (2004) 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. http://dx.doi.org/10.1182/blood-2003-07-2520
Uitte de, W.S.,
Van, M.V.,
Rosendaal, F.R.,
Vos, H.L.,
De Visser, M.C. and Bertina, R.M. (2004) Haplotypes
of the EPCR Gene, Plasma sEPCR Levels and the Risk of Deep Venous Thrombosis. Journal of Thrombosis and Haemostasis, 2, 1305-1310. http://dx.doi.org/10.1046/j.1538-7836.2004.00855.x
Karabiyik, A., Yilmaz, E., Egin, Y.
and Akar, N. (2012) The Effects of Endothelial Protein C Receptor
Gene Polymorphisms on the Plasma sEPCR Level in Venous Thrombosis Patients. Turkish Journal of Hematology, 29, 55-62.
Ducros, E., Mirshahi, S.S., Faussat, A.M., Mirshahi, P., Dimicoli, S., Tang, R., et al. (2012)
Soluble Endothelial Protein C Receptor (sEPCR) Is Likely a Biomarker of Cancer-Associated
Hypercoagulability in Human Hematologic Malignancies. Cancer Medicine, 1, 261-267. http://dx.doi.org/10.1002/cam4.11
Abd-Elghfaar, A.A., Ismail, M.M., Farweez, B.A. and Elmasry, R.F. (2013) Influence of Soluble Endothelial Protein C Receptor
(sEPCR) on Hypercoagulable State of Haemodialysis Patients. International Journal of Science and
Research, 4, 1123-1128.
Miller, S.A.,
Dykes, D.D. and Polesky, H.F. (1988) A
Simple Salting out Procedure for Extracting DNA from Human Nucleated Cells. Nucleic Acids Research, 16, 1215. http://dx.doi.org/10.1093/nar/16.3.1215
Muleledhu, A.L.,
Galukande, M.,
Makobore, P.,
Mwambu, T., Ameda, F. and Kiguli-Malwadde, E. (2013) Deep Venous Thrombosis after Major Abdominal
Surgery in a Ugandan Hospital: A Prospective Study. International Journal of Emergency Medicine, 6, 43. http://dx.doi.org/10.1186/1865-1380-6-43
Fall, A.O.T.,
Proulle, V.,
Sall, A.,
Mbaye, A.,
Samba Ba, P.,
Diao, M., et al. (2014) Risk Factors for Thrombosis in an African
Population. Clinical Medical Insights: Blood Disorders, 7, 1-6.
Yin, G.,
Jin, X.,
Ming, H.,
Zheng, X. and Zhang, D. (2012)
Endothelial Cell Protein C Receptor Gene 6936A/G Polymorphism Is Associated
with Venous Thromboembolism. Experimental
and Therapeutic Medicine, 3, 989-992.
Chen, X.D.,
Tian, L.,
Li, M.,
Jin, W.,
Zhang, H.K. and Zheng, C.F. (2011)
Relationship between Endothelial Cell Protein C Receptor Gene 6936A/G Polymorphisms
and Deep Venous Thrombosis. Chinese
Medical Journal, 124, 72-75.
Navarro, S.,
Medina, P.,
Mira, Y.,
Estelles, A.,
Villa, P.,
Ferrando, F., et al. (2008) Haplotypes of the EPCR Gene, Prothrombin
Levels, and the Risk of Venous Thrombosis in Carriers of the Prothrombin
G20210A Mutation. Haematologica, 93, 885-891. http://dx.doi.org/10.3324/haematol.12448
Chen, X.D.,
Tian, L.,
Zheng, C.F.,
Li, M.,
Jin, W.,
Wang, X.H., et al. (2010) Relationship between Endothelial Protein C
Receptor Gene 6936A/G Polymorphisms and Deep Venous Thrombosis. Chinese Journal of Hematology, 31, 607- 609.
Dennis, J.,
Johnson, C.Y.,
Adediran, A.S., de
Andrade, M.,
Heit, J.A.,
Morange, P.E., et al. (2012) The Endothelial Protein C Receptor (PROCR)
Ser219Gly Variant and Risk of Common Thrombotic Disorders: A HuGE Review and
Meta-Analysis of Evidence from Observational Studies. Blood, 119, 2392-2400. http://dx.doi.org/10.1182/blood-2011-10-383448
Yamagishi, K.,
Cushman, M.,
Heckbert, S.R.,
Tsai, M.Y. and Folsom, A.R. (2009)
Lack of Association of Soluble Endothelial Protein C Receptor and PROCR 6936A/G Polymorphism with the Risk of Venous Thromboembolism in a Prospective
Study. British Journal of Haematology, 145, 221-226. http://dx.doi.org/10.1111/j.1365-2141.2009.07612.x
Medina, P.,
Navarro, S.,
Estelles, A.,
Vaya, A.,
Woodhams, B.,
Mira, Y., et al. (2004) Contribution of Polymorphisms in the
Endothelial Protein C Receptor Gene to Soluble Endothelial Protein C Receptor
and Circulating Activated Protein C Levels, and Thrombotic Risk. Thrombosis and Haemostasis, 91, 905-911. http://dx.doi.org/10.1160/th03-10-0657
Qu, D.,
Wang, Y.,
Song, Y.,
Esmon, N.L. and Esmon, C.T. (2006)
The Ser219-->Gly Dimorphism of the Endothelial Protein C Receptor
Contributes to the Higher Soluble Protein Levels Observed in Individuals with
the A3 Haplotype. Journal of Thrombosis
and Haemostasis, 4, 229-235. http://dx.doi.org/10.1111/j.1538-7836.2005.01676.x
Saposnik, B.,
Lesteven, E.,
Lokajczyk, A.,
Esmon, C.T.,
Aiach, M. and Gandrille, S. (2008) Alternative mRNA Is Favored by the A3 Haplotype
of the EPCR Gene PROCR and Generates a Novel Soluble form of EPCR in
Plasma. Blood, 111, 3442-3451. http://dx.doi.org/10.1182/blood-2007-08-104968
Medina, P.,
Navarro, S.,
Estelles, A.,
Vaya, A.,
Bertina, R.M. and Espana, F. (2005)
Influence of the 4600A/G and 4678G/C Polymorphisms in the Endothelial Protein C
Receptor (EPCR) Gene on the Risk of Venous Thromboembolism in Carriers of
Factor V Leiden. Thrombosis and
Haemostasis, 94, 389-394.
Espana, F., Medina, P., Navarro, S., Estelles, A. and Aznar, J. (2002) Inherited Abnormalities in the Protein C Activation
Pathway. Pathophysiology of Haemostasis
and Thrombosis, 32, 241-244. http://dx.doi.org/10.1159/000073573