title: PROC c.574_576del polymorphism: a common genetic risk factor for venous thrombosis in the Chinese population.
abstract: 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.
  
  
  OBJECTIVE
  To identify possible common abnormal factors that could contribute to thrombosis susceptibility.
  
  
  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%.
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Hubei, China.
authors: L
authors: L
authors: Tang
authors: X
authors: X
authors: Lu
authors: J M
authors: JM
authors: Yu
authors: Q Y
authors: QY
authors: Wang
authors: R
authors: R
authors: Yang
authors: T
authors: T
authors: Guo
authors: H
authors: H
authors: Mei
authors: Y
authors: Y
authors: Hu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D044466:Asian People / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000235:genetics*; D001780:Blood Coagulation Tests; D019556:COS Cells; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011486:Protein C / Q000235:genetics* / Q000378:metabolism; D020151:Protein C Deficiency / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D014162:Transfection; D020246:Venous Thrombosis / Q000097:blood / Q000208:ethnology / Q000235:genetics*
chemical_list: D015415:Biomarkers; D011486:Protein C