Genetic regulation of plasma levels of vitamin K-dependent proteins involved in hematostatis: results from the GAIT Project. Genetic Analysis of Idiopathic Thrombophilia

Thromb Haemost. 2001 Jan;85(1):88-92.


Vitamin K-dependent proteins play a critical role in hemostasis. We have analysed the genetic and environmental correlations between measures of several vitamin K-dependent proteins in 21 Spanish extended families, including 397 individuals. Plasma functional levels of factors II, VII, IX, X, protein C and functional protein S were assayed in an automated coagulometer. Antigenic levels of total and free protein S were measured using an ELISA method. A maximum likelihood-based covariance decomposition analysis was used to assess the heritability of each trait and the genetic and environmental correlations between all possible pairs. All of the plasma levels had a significant genetic component (heritability) ranging from 22% to 52% of the phenotypic variance. Among the 28 possible pairs of genetic correlations, 18 were significant at a level of p < 0.05 and six exhibited a p-value between 0.05 and 0.10. Positive environmental correlation was observed for 25 of the pairs (p < 0.05). We conclude that genetic effects account for a large proportion of the observed phenotypic variation in vitamin K-dependent proteins. Some of the genes appear to pleiotropically influence all of these traits, since most pairs of phenotypes exhibit significant genetic correlation. However, since these phenotypes show a high degree of environmental correlation, it is also likely that the same environmental factors influence them co-jointly.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Blood Coagulation Factors / drug effects
  • Blood Coagulation Factors / genetics
  • Blood Coagulation Factors / metabolism*
  • Child
  • Child, Preschool
  • Contraceptives, Oral / blood
  • Contraceptives, Oral / pharmacology
  • Factor X / genetics
  • Factor X / metabolism
  • Family Health
  • Female
  • Gene Expression Regulation / genetics*
  • Hemostasis / drug effects
  • Hemostasis / genetics*
  • Hispanic or Latino / genetics
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Phenotype
  • Protein S / genetics
  • Protein S / metabolism
  • Sex Factors
  • Smoking / adverse effects
  • Smoking / blood
  • Vitamin K / pharmacology*


  • Blood Coagulation Factors
  • Contraceptives, Oral
  • Protein S
  • Vitamin K
  • Factor X