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Polymorphisms in the protein C gene as risk factor for venous thrombosis

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: http://dx.doi.org/10.1160/TH08-08-0502
Issue: 2009: 101/1 (Jan) pp. 1-216
Pages: 62-67
Ahead of Print: ###MANUSCRIPT_aheadofprint###

Polymorphisms in the protein C gene as risk factor for venous thrombosis

Elisabeth R. Pomp1; Carine J. M. Doggen1; Hans L. Vos2,3; Pieter H. Reitsma2,3; Frits R. Rosendaal1–3
1Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; 2Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; 3Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands

Keywords

Risk Factors, Venous thrombosis, polymorphisms, Protein C, case-control study

Summary

Protein C is an important inhibitor of blood coagulation. We investigated the effect of two polymorphisms within the promoter region of the protein C gene (C/T at position 2405 and A/G at position 2418) on risk of venous thrombosis and on plasma protein C levels. In addition the combined effect of the two polymorphisms with factor V Leiden and oral contraceptive use was investigated. Previous studies on these polymorphisms were small and were not able to investigate synergistic effects. In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), protein C levels were determined in 2,043 patients with venous thrombosis and 2,857 control subjects, and the two polymorphisms in 4,285 patients and 4,863 control subjects. The CC/GG genotype was associated with the lowest protein C levels. Compared to carriers of the TT/AA genotype – a genotype associated with higher protein C levels – the risk of venous thrombosis in CC/GG carriers was 1.3-fold increased (95% confidence interval 1.09–1.48). The combination of factor V Leiden with the CC/GG genotype led to a 4.7-fold increased risk, compared to non-carriers with the TT/AA genotype. Oral contraceptive use together with the CC/ GG genotype resulted in a 5.2-fold increased risk. In conclusion, the CC/GG genotype is associated with lower levels of protein C and an elevated risk of venous thrombosis compared to the TT/AA genotype. There is no clear synergistic effect of the CC/ GG genotype with factor V Leiden or oral contraceptive use on thrombotic risk.

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