Genetic regulation of plasma levels of vitamin K-dependent proteins involved in hematostatis: results from the GAIT Project. Genetic Analysis of Idiopathic Thrombophilia.
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.
Souto
J C
JC
Unitat d'Hemostàsia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. jsouto@hsp.santpau.es
Almasy
L
L
Blangero
J
J
Stone
W
W
Borrell
M
M
Urrutia
T
T
Mateo
J
J
Fontcuberta
J
J
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001779:Blood Coagulation Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003276:Contraceptives, Oral / Q000097:blood / Q000494:pharmacology; D005170:Factor X / Q000235:genetics / Q000378:metabolism; D005192:Family Health; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006487:Hemostasis / Q000187:drug effects / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017293:Protein S / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects / Q000097:blood; D014812:Vitamin K / Q000494:pharmacology*
D001779:Blood Coagulation Factors; D003276:Contraceptives, Oral; D017293:Protein S; D014812:Vitamin K; D005170:Factor X