UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

FVII, FVIIa, and Downstream Markers of Extrinsic Pathway Activation Differ by EPCR Ser219Gly Variant in Healthy Men

Ireland, HA; Cooper, JA; Drenos, F; Acharya, J; Mitchell, JP; Bauer, KA; ... Humphries, SE; + view all (2009) FVII, FVIIa, and Downstream Markers of Extrinsic Pathway Activation Differ by EPCR Ser219Gly Variant in Healthy Men. ARTERIOSCL THROM VAS , 29 (11) 1968 - 1974. 10.1161/ATVBAHA.109.191551. Gold open access

Abstract

Objective-The purpose of this study was to determine the effect of a variant in EPCR (Ser219Gly), previously shown to affect EPCR shedding, on plasma FVII, FVIIa, and downstream markers of activated coagulation.Methods and Results-Statistical analysis was undertaken in approximate to 2000 healthy middle aged men (NPHSII). Higher soluble EPCR levels were confirmed for Gly allele carriers (P<0.0001). Significantly higher levels of FVII, FVIIa, and downstream markers of activated coagulation in the extrinsic pathway ( FIX activation pep [FIXpep]; FX activation pep [FXpep]), and prothrombin F1+2 (F1+2) were identified in baseline samples, in Gly carriers compared to Ser/Ser (P<=0.04 for trend). In repeat samples collected for up to 5 years, levels of FVII and F1+2 were higher in Gly allele carriers compared to Ser/Ser by (FVII: 6.9% CI 5.5 to 8.4 in Ser/Gly; and 23.4% CI 16.3 to 30.8 in Gly/Gly, P<0.0001), (F1+2: 8.1% CI 5.2 to 11.1 in Ser/Gly; 25.2% CI 11.8 to 40.3 in Gly/Gly, P<0.04), confirming reproducibility of findings at baseline. Molar ratios for FIXpep, FXpep, and F1+2 to FVIIa were constant in Ser/Ser and Ser/Gly but tended to be higher in Gly/Gly, reaching statistical significance for FIXpep: FVIIa (P=0.04).Conclusions-These data suggest that higher levels of FVII and FVIIa circulate when EPCR shedding is greatest. Furthermore, these results suggest consequences for activation of extrinsic coagulation. (Arterioscler Thromb Vasc Biol. 2009; 29:1968-1974.)

Type:Article
Title:FVII, FVIIa, and Downstream Markers of Extrinsic Pathway Activation Differ by EPCR Ser219Gly Variant in Healthy Men
Open access status:An open access publication
DOI:10.1161/ATVBAHA.109.191551
Publisher version:http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC2775706/?tool=pubmed
Keywords:endothelial protein C receptor, FVIIa, extrinsic coagulation, FIX activation peptide, FX activation peptide, prothrombin F1+2, PROTEIN-C RECEPTOR, CORONARY-HEART-DISEASE, FACTOR-VII ACTIVATION, A3 HAPLOTYPE, PLASMA, RISK, GENE, INFLAMMATION, COAGULATION, SEPCR
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science

Archive Staff Only: edit this record