Genetics of hemostasis: differential effects of heritability and household components influencing lipid concentrations and clotting factor levels in 282 pediatric stroke families.
BACKGROUND
The identification of heritable and environmental factors possibly influencing a condition at risk should be a prerequisite for the search for the proportion of variance attributable for shared environmental effects (c(2)) modulating the risk of disease. Such epidemiologic approaches in families with a first acute ischemic stroke during early childhood are lacking.


OBJECTIVE
Our goal was to estimate the phenotypic variation within lipid concentrations and coagulation factor levels and to estimate the proportions attributable to heritability (h(2)r) and c(2) in pediatric stroke families.


METHODS
Blood samples were collected from 1,002 individuals from 282 white stroke pedigrees. We estimated h(2)r and c(2) for lipoprotein (a) [Lp(a)], cholesterol, high-density lipoprotein, low-density lipoprotein (LDL), fibrinogen, factor (F) II, FV, FVIIIC, von Willebrand factor (vWF), antithrombin, protein C, protein S, plasminogen, protein Z, total tissue factor pathway inhibitor (TFPI), prothrombin fragment F1.2, and D-dimer, using the variance component method in sequential oligogenetic linkage analysis routines.


RESULTS
When incorporating h(2)r and c(2) in one model adjusted for age, blood group, sex, smoking, and hormonal contraceptives, significant h(2)r estimates were found for Lp(a), LDL, fibrinogen, protein C, and protein Z. In addition to the significant h(2)r estimates, c(2) showed a significant effect on phenotypic variation for fibrinogen, protein C, and protein Z. A significant c(2) effect was found for cholesterol, and plasma levels of FII, FV, vWF, antithrombin, protein S, plasminogen, and TFPI, ranging from 9.3% to 33.2%.


CONCLUSIONS
Our research stresses the importance of research on the genetic variability and lifestyle modifications of risk factors associated with pediatric stroke.
Department of Pediatric Hematology/Oncology, University of Münster, Münster, Germany. leagottl@uni-muenster.de
Ulrike
U
Nowak-Göttl
Claus
C
Langer
Sandra
S
Bergs
Sabine
S
Thedieck
Ronald
R
Sträter
Monika
M
Stoll
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001779:Blood Coagulation Factors / Q000235:genetics / Q000378:metabolism*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D005165:Factor V / Q000235:genetics / Q000378:metabolism; D005192:Family Health; D005260:Female; D006487:Hemostasis; D006801:Humans; D007223:Infant; D008055:Lipids / Q000097:blood*; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011486:Protein C / Q000378:metabolism; D017293:Protein S / Q000378:metabolism; D011516:Prothrombin / Q000235:genetics / Q000378:metabolism; D012907:Smoking; D020521:Stroke / Q000097:blood* / Q000235:genetics
D001779:Blood Coagulation Factors; D008055:Lipids; D017270:Lipoprotein(a); D011486:Protein C; D017293:Protein S; D005165:Factor V; D011516:Prothrombin; D002784:Cholesterol