Genetics of hemostasis: differential effects of heritability and household components influencing lipid concentrations and clotting factor levels in 282 pediatric stroke families.

Abstract

BackgroundThe 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 (c2) modulating the risk of disease. Such epidemiologic approaches in families with a first acute ischemic stroke during early childhood are lacking.ObjectivesOur goal was to estimate the phenotypic variation within lipid concentrations and coagulation factor levels and to estimate the proportions attributable to heritability (h2r) and c2 in pediatric stroke families.MethodsBlood samples were collected from 1,002 individuals from 282 white stroke pedigrees. We estimated h2r and c2 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.ResultsWhen incorporating h2r and c2 in one model adjusted for age, blood group, sex, smoking, and hormonal contraceptives, significant h2r estimates were found for Lp(a), LDL, fibrinogen, protein C, and protein Z. In addition to the significant h2r estimates, c2 showed a significant effect on phenotypic variation for fibrinogen, protein C, and protein Z. A significant c2 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%.ConclusionsOur research stresses the importance of research on the genetic variability and lifestyle modifications of risk factors associated with pediatric stroke.