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Keywords:

  • genetic risk factor;
  • polymorphism;
  • protein C;
  • venous thrombosis

See also Hamasaki N. Unmasking Asian thrombophilia: is APC dysfunction the real culprit? This issue, pp 2016–8.

Summary.  Background:  There are ethnic differences in the genetic risk factors for venous thrombosis (VT). The genetic causes of VT in the Chinese population are not fully understood.

Objectives:  To identify possible common abnormal factors that could contribute to thrombosis susceptibility.

Methods/Results:  We measured the levels of nine types of plasma coagulation factor, three types of anticoagulation factor and two types of fibrinolytic factor in 310 VT patients. Factor V activity was higher in 32 cases. Eleven of the 32 cases also had low protein C (PC) or protein S (PS) activities, indicating PC or PS deficiency. No other abnormalities were observed in the other 21 cases. All of the samples were sensitive to activated PC inactivation. Therefore, the abnormal factor involved may be FV inactivator or its cofactor rather than FV itself. Resequencing identified a common PROC c.574_576del variant in 10 of the 32 subjects. In a case–control study, this variant was detected in 68 of the 1003 patients and in 25 of the 1031 controls. It had an adjusted odds ratio of 2.71 (95% confidence interval [CI] 1.68–4.36). PC amidolytic activities of most variant carriers were similar to those of non-carriers, but the mean anticoagulant activity was only 72.7 U dL−1. Expression studies in vitro showed that the anticoagulant activity of the mutant PC was 43.6% of that of the wild-type PC.

Conclusions:  We identified what is, so far, the most common genetic risk factor for VT in the Chinese population, with its prevalence being approximately 2.36%.