title: Normal ranges and genetic variants of antithrombin, protein C and protein S in the general Chinese population. Results of the Chinese Hemostasis Investigation on Natural Anticoagulants Study I Group.
abstract: BACKGROUND
  Inherited deficiency of antithrombin, protein C and protein S, three important, naturally occurring coagulation inhibitors, might play a major role in the occurrence of venous thromboembolism in Chinese. The establishment of age- and gender-related normal ranges of these inhibitors is crucial for an accurate diagnosis of these deficiencies.
  
  
  METHODS
  We designed a prospective cross-sectional study recruiting healthy adults from four university-affiliated hospitals in China. Antithrombin, protein C and protein S were studied by measuring their activity. Gene analysis was performed when natural anticoagulant deficiency was suspected. Polymorphisms of the factor V gene were searched for among subjects who were positive for activated protein C resistance.
  
  
  RESULTS
  In 3493 healthy Chinese adults (1734 men, 1759 women; age 17-83 years), we found higher age-adjusted activities for protein C and protein S in men than in women but no sex difference for antithrombin. In women, mean protein C and protein S activities increased with age. In men, mean protein C levels increased with age up to the age of 49 but decreased after 50 years old; mean protein S levels decreased after 50 years of age. Antithrombin levels remained stable over time in women but decreased significantly after 50 years of age in men. Reference values according to age and sex allowed the identification of 15 genetic variants (protein C:10, antithrombin:3, protein S:2) in subjects with protein activity below the 1(st) percentile.
  
  
  CONCLUSIONS
  This is the largest survey ever conducted in the healthy general Chinese population. These normal ranges provide the essential basis for the diagnosis and treatment of thrombosis in Chinese.
authors.affiliation: Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 100730 Beijing, China.
authors.forename: Tienan
authors.initials: T
authors.lastname: Zhu
authors.forename: Qiulan
authors.initials: Q
authors.lastname: Ding
authors.forename: Xia
authors.initials: X
authors.lastname: Bai
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Florentia
authors.initials: F
authors.lastname: Kaguelidou
authors.forename: Corinne
authors.initials: C
authors.lastname: Alberti
authors.forename: Xuqian
authors.initials: X
authors.lastname: Wei
authors.forename: Baolai
authors.initials: B
authors.lastname: Hua
authors.forename: Renchi
authors.initials: R
authors.lastname: Yang
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.forename: Zhaoyue
authors.initials: Z
authors.lastname: Wang
authors.forename: Changgeng
authors.initials: C
authors.lastname: Ruan
authors.forename: Nicole
authors.initials: N
authors.lastname: Schlegel
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D058833:Antithrombin Proteins / Q000235:genetics* / Q000378:metabolism*; D002681:China; D003430:Cross-Sectional Studies; D005260:Female; D006487:Hemostasis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D011486:Protein C / Q000235:genetics* / Q000378:metabolism; D017293:Protein S / Q000235:genetics* / Q000378:metabolism; D012016:Reference Values; D012737:Sex Factors; D055815:Young Adult
chemical_list: D058833:Antithrombin Proteins; D011486:Protein C; D017293:Protein S