title: Three polymorphisms in promoter of protein C gene with endothelial protein c receptor gene and risk of venous thrombosis.
abstract: The primary abnormalities that are associated with a risk of venous thrombosis are the deficiencies of protein C. Protein C (PROC), encoded by the PROC gene, acts through its affinity for binding to its transmembrane endothelial cell protein C receptor (EPCR) encoded by the EPCR gene. The objective of the study was to analyze the link between three polymorphisms in the promoter of PROC gene, the polymorphism in the EPCR gene and the occurrence of venous thrombosis. We genotyped 135 individuals - 51 cases with documented venous thrombosis and 84 healthy volunteers without a history of venous thrombosis. The occurrence of the TAA haplotype of PROC gene was significantly more frequent in the controls (N = 48; 57.1%), compared with the patients (N = 18; 35.3%), (P = 0.0206). The healthy individuals were also significantly often carriers of the TAA haplotype and the standard genotype AA of EPCR gene (50 vs. 25.5%) than the patients (P = 0.0066). The frequency of haplotypes CAA and CGT of PROC gene was insignificantly higher in the patients (15.7 and 21.6%, respectively) than in the control group (9.5 and 13.1%). The combination of haplotype CAA/CAA of PROC gene and variant genotype AG of EPCR gene was confirmed with a higher frequency in the group of patients (3.9 vs. 1.2%).This analysis showed that the PROC haplotype associated with a high protein C level (TAA) and the EPCR AA genotype was significantly more frequent in the healthy volunteers (P = 0.0066). Haplotypes associated with a low production of protein C (CAA or CGT) were more frequent in patients with venous thrombosis.
authors.affiliation: aDepartment of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno bVascular Unit, Health centre Zahradnikova, Brno, The Czech Republic.
authors.forename: Kristyna
authors.initials: K
authors.lastname: Horakova
authors.forename: Michal
authors.initials: M
authors.lastname: Kolorz
authors.forename: Ladislava
authors.initials: L
authors.lastname: Bartosova
authors.forename: Vaclav
authors.initials: V
authors.lastname: Pechacek
authors.forename: Katerina
authors.initials: K
authors.lastname: Wroblova
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics*; D016022:Case-Control Studies; D000074283:Endothelial Protein C Receptor; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011486:Protein C / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D012307:Risk Factors; D020246:Venous Thrombosis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011486:Protein C; D011956:Receptors, Cell Surface