Association Between Gene Polymorphism Of Endothelial Cell Protein C Receptor And Thrombotic Diseases In Chinese Han Population Of Hubei District

PartⅠAssociation between gene polymorphism of endothelial cell protein C receptor and deep venous thrombosis in Chinese Han population of Hubei districtObjective To ascertain the frequency of endothelial cell protein C receptor (EPCR) gene A6936G variant and to study the association between this mutation and deep venous thrombosis (DVT) in Chinese Han population of Hubei district; to investigate the associations between plasma activated protein C (APC) levels and DVT patients with different genotypes.Methods The genotype and allele frequencies of EPCR A6936G were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 110 DVT patients and 380 healthy Chinese Han persons. The genotype and allele frequencies were calculated and analyzed. Levels of circulating APC were measured using a chromogenic substrate assay.Results 1. A total of 110 DVT patients were evaluated, including 39 primary DVT patients and 71 secondary DVT patients. The genotype frequencies of A6936G AA, AG and GG genotypes in DVT group were 64.6%, 33.6% and 1.8%, respectively. While in control group of 380 healthy persons, the frequencies of AA and AG genotypes were 88.2% and 11.8%, there was no GG genotype. The mutant genotype (AG+GG) frequency in DVT patients was 35.4% (OR: 4.089, 95%CI: 2.538~6.588) and the mutant allele (G) frequency in DVT patients was 18.6% (OR: 3.639, 95%CI: 2.364~5.601), which were both significantly higher than those in control group (11.8% and 5.9%, respectively, P=0.0001, P=0.0001). 2. The plasma APC levels in DVT patients with different genotypes of EPCR A6936G AA, AG and GG were obviously lower than those in control group (F=12.79,P=0.0005). The plasma APC levels in DVT patients with mutant genotypes (AG+GG) were lower than that in DVT patients with AA genotype, but there was no significant difference(P>0.05). 3. The mutant genotype frequency in secondary DVT patients was lower than that in primary DVT patients (35.2% vs35.9%), and the mutant allele frequency in secondary DVT patients was higher than that in primary DVT patients (19.0% vs17.9%), but these differences were not of significance (P>0.05). The plasma APC levels in secondary DVT patients with different EPCR genotypes were higher than those in primary DVT patients, but these differences were not of significance (P>0.05).Conclusion A6936G polymorphism of EPCR can be detected in Chinese Han population of Hubei district, which may be associated with the increase risk of thrombosis for DVT patients. The plasma APC level in Chinese Han DVT population in Hubei district was significantly lower than that in control group, which indirectly indicated that the plasma soluble EPCR (sEPCR) level in DVT patients was significantly higher than that in control group, so the higher sEPCR level in plasma may be associated with the increased risk of venous thrombosis. EPCR A6936G polymorphism may not be the risk factor independent of known DVT risk factors such as trauma, increased blood viscosity.PartⅡAssociation between gene polymorphism of endothelial cell protein C receptor and cerebral infarction in Chinese Han population of Hubei districtObjective To ascertain the frequency of endothelial cell protein C receptor (EPCR) gene A6936G variant and to study the association between this mutation and cerebral infarction in Chinese Han population of Hubei district; to investigate the associations between plasma activated protein C (APC) levels and cerebral infarction patients with different genotypes.Methods The genotype and allele frequencies of EPCR A6936G were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 380 cerebral infarction patients and 380 healthy Chinese Han persons. The genotype and allele frequencies were calculated and analyzed. Levels of circulating APC were measured using a chromogenic substrate assay.Results 1. A total of 380 cerebral infarction patients were evaluated, including 208 men and 172 women. The genotype frequencies of A6936G AA, AG and GG genotypes in cerebral infarction group were 77.1%, 22.1% and 0.8%, respectively. While in control group of 380 healthy persons, the frequencies of AA and AG genotypes were 88.2% and 11.8%, there was no GG genotype. The mutant genotype (AG+GG) frequency in cerebral infarction patients was 22.9% (OR: 2.210, 95%CI: 1.502~3.253) and the mutant allele (G) frequency in cerebral infarction patients was 11.8% (OR: 2.134, 95%CI: 1.480~3.078), which were both significantly higher than those in control group (11.8% and 5.9%, respectively, P=0.002, P=0.003). 2. The plasma APC levels in cerebral infarction patients with different genotypes of EPCR A6936G AA, AG and GG were obviously lower than those in control group (F=12.76,P=0.0005). The plasma APC levels in cerebral infarction patients with mutant genotypes were lower than that in cerebral infarction patients with AA genotype, but there was no significant difference(P>0.05). 3. The mutant genotype frequency and mutant allele frequency in male cerebral infarction patients were significantly higher than those in female patients (32.2% vs11.6%, 16.6% vs5.5%, P=0.001, P=0.001, respectively). The plasma APC levels in male cerebral infarction patients with different EPCR genotypes were higher than those in female patients, but these differences were not of significance (P>0.05).Conclusion A6936G polymorphism of EPCR can be detected in Chinese Han population of Hubei district, which may be associated with the increase risk of thrombosis for cerebral infarction patients. The plasma APC level in Chinese Han cerebral infarction population in Hubei district was significantly lower than that in control group, which indicated indirectly that the plasma soluble EPCR (sEPCR) level in cerebral infarction patients was significantly higher than that in control group, so the higher sEPCR level in plasma may be associated with the increased risk of thrombosis. The distribution of the EPCR A6936G polymorphism may be sex-related in Chinese Han cerebral infarction population in Hubei district.PartⅢAssociation between gene polymorphism of endothelial cell protein C receptor and coronary heart disease in Chinese Han population of Hubei districtObjective To ascertain the frequency of endothelial cell protein C receptor (EPCR) gene A6936G variant and to study the association between this mutation and coronary heart disease (CHD) in Chinese Han population of Hubei district; to investigate the associations between plasma activated protein C (APC) levels and CHD patients with different genotypes.Methods The genotype and allele frequencies of EPCR A6936G were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 300 CHD patients and 380 healthy Chinese Han persons. The genotype and allele frequencies were calculated and analyzed. Levels of circulating APC were measured using a chromogenic substrate assay.Results 1. A total of 300 CHD patients were evaluated, including 172 patients with a history of hypertension and 128 patients without a history of hypertension. The genotype frequencies of A6936G AA, AG and GG genotypes in CHD group were 73.3%,26.0% and 0.7%, respectively. While in control group of 380 healthy persons, the frequencies of AA and AG genotypes were 88.2% and 11.8%, there was no GG genotype. The mutant genotype (AG+GG) frequency in CHD patients was 26.7% (OR: 2.707, 95%CI: 1.826~4.014) and the mutant allele (G) frequency in CHD patients was 13.7% (OR: 2.515, 95%CI: 1.736~3.644), which were both significantly higher than those in control group (11.8% and 5.9%, respectively, P=0.001, P=0.001). 2. The plasma APC levels in CHD patients with different genotypes of EPCR A6936G AA, AG and GG were obviously lower than those in control group (F=12.77,P=0.0005). The plasma APC levels in CHD patients with mutant genotypes were lower than that in CHD patients with AA genotype, but there was no significant difference(P>0.05). 3. The mutant genotype frequency and mutant allele frequency in CHD patients with a history of hypertension were lower than those in patients without a history of hypertension (26.2% vs27.3%, 13.4% vs14.1%, respectively), but these differences were not of significance (P>0.05). The plasma APC levels in CHD patients with a history of hypertension were higher than thoses in patients without a history of hypertension (P>0.05)。Conclusion A6936G polymorphism of EPCR can be detected in Chinese Han population of Hubei district, which may be associated with the increase risk of thrombosis for CHD patients. The plasma APC level in Chinese Han CHD population in Hubei district was significantly lower than that in control group, which indirectly indicated that the plasma soluble EPCR (sEPCR) level in CHD patients was significantly higher than that in control group, so the higher sEPCR level in plasma may be associated with the increased risk of thrombosis of coronary arteries. EPCR A6936G polymorphism may not be the risk factor independent of hypertension, the known CHD risk factor.