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

Pilar Medina; Silvia Navarro; Amparo Estellés; Amparo Vayá; Rogier M. Bertina; Francisco España

doi:10.1160/TH05-02-0089

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 94(02): 389-394
DOI: 10.1160/TH05-02-0089

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

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

Authors

Pilar Medina

¹Research Center, Valencia, Spain
Silvia Navarro

¹Research Center, Valencia, Spain
Amparo Estellés

¹Research Center, Valencia, Spain
Amparo Vayá

²Department of Clinical Pathology, La Fe University Hospital, Valencia, Spain
Rogier M. Bertina

³Hemostasis and Thrombosis Research Centre, Department of Hematology, Leiden University Medical Centre, Leiden, The Netherlands
Francisco España

¹Research Center, Valencia, Spain

Abstract

Summary

Two polymorphisms in the endothelial protein C receptor (EPCR) gene, 4600A/G and 4678G/C, have been reported to influence the risk of venous thromboembolism (VTE). The objective of this study was to assess whether these polymorphisms modify the risk of VTE in carriers of factor V (FV) Leiden. We genotyped 295 carriers of FV Leiden for these polymorphisms: 100 unrelated patients with a history ofVTE (propositi) and 195 relatives (14 of them symptomatic) of 81 of the propositi. Spontaneous VTE events occurred in 71% of propositi carrying the 4678GG genotype, 65% carrying the GC, and 43% with the CC genotype. The mean age at the first onset was significantly higher in propositi carrying the 4678CC than in those with the GC or GG genotype (p=0.046). Among the 276 carriers of FV Leiden from the 81 families studied, the 95 symptomatic members had similar 4600G allele and 4600AG genotype frequencies but significantly lower 4678C allele (p=0.002) and 4678CC genotype (p=0.004) frequencies than the 181 asymptomatic members. The probability of being free of thrombosis at age 40 was significantly higher in the 66 carriers of the 4678CC genotype (94%) than in the 138 carrying the GC (72%) or in the 72 with the 4678GG genotype (60%) (p<0.001). Multivariate analysis showed that the 4678CC genotype reduced the risk of thrombosis in carriers of FV Leiden (OR=0.31;95% CI=0.16–0.83). The incidence ofVTE was higher in the 195 relatives with FV Leiden than in the 133 without FV Leiden (OR=4.7; CI=1.3–7.2). These results show that carriers of FV Leiden with the 4678CC genotype have a significantly reduced risk of VTE compared with those carrying the 4678GG or GC genotype, probably due to the higherAPC levels previously observed in individuals carrying the 4678CC genotype.

Keywords

Endothelial protein C receptor - factor V Leiden - venous thromboembolism - polymorphisms - survival time - interaction

Full Text

References

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