Endothelial cell protein C receptor gene 6936A/G and 4678G/C polymorphisms as risk factors for deep venous thrombosis.
Endothelial cell protein C receptor (EPCR) enhances the generation of activated protein C by the thrombin-thrombomodulin complex. A soluble form of EPCR (sEPCR) is present in plasma. Two polymorphisms in the EPCR gene (6936A/G and 4678G/C) have been reported to influence the risk of venous thromboembolism. We aimed to investigate the relation between EPCR gene polymorphisms (6936A/G and 4678C/G) and deep venous thrombosis (DVT) and their relations to sEPCR level. This study involved 90 patients with DVT and 90 age and sex-matched healthy controls. Plasma levels of sEPCR were measured in 45 cases of the primary DVT by ELISA. PCR-restriction fragment length polymorphism (RFLP) was used for detection of EPCR polymorphisms (6936A/G and 4678G/C). Regarding 6936A/G, our results demonstrated that mutant genotypes (AG, GG) were associated with an increased risk for DVT [P < 0.001, odds ratio (OR) 4.125, 95% confidence interval (95% CI) 2.198-7.740] as well as its mutant allele G (P < 0.001, OR 2.549, 95% CI 1.601-4.061). The mutant genotypes were associated with increased levels of sEPCR. Although in 4678G/C, our results demonstrated that the mutant genotype (CC) was considered as a protective factor against DVT (P = 0.014, OR 0.289, 95% CI 0.108-0.776) as well as its mutant allele C (P = 0.02, OR 0.600, 95% CI 0.388-0.927), but it had no effect on sEPCR level. Our data suggest that 6936A/G polymorphism is a risk factor for DVT and is associated with elevated plasma levels of sEPCR, while 4678G/C polymorphism plays a role in protection against DVT.
aDepartment of Clinical and Chemical Pathology bDepartment of General Surgery, Faculty of Medicine, Cairo University, Giza, Egypt.
Naguib
N
Zoheir
Nabiel
N
Eldanasouri
Asmaa A
AA
Abdel-Aal
Karim Adel
KA
Hosny
Wafaa M
WM
Abdel-Ghany
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood / Q000235:genetics*; D000074283:Endothelial Protein C Receptor; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D011956:Receptors, Cell Surface / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology / Q000235:genetics*; D055815:Young Adult
D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011956:Receptors, Cell Surface