title: Phenotypic sensitivity to activated protein C in healthy families: importance of genetic components and environmental factors.
abstract: The relative importance of environmental factors and genetic components other than factor V Leiden on the sensitivity to activated protein C (APC) in healthy nuclear families was determined. We studied 149 European families (298 parents and 278 biological offspring aged more than 6 years). APC response was measured and expressed as normalized APC-sensitivity ratio (n-APC-SR). Subjects were genotyped for G1691A and G20210A polymorphisms of factor V and II genes; levels of factors II, V and VIII, antithrombin, cholesterol, high-density lipoprotein cholesterol and triglycerides were measured. After identifying variables influencing the n-APC-SR by a stepwise multiple regression model, variance component analysis was used. The heritability (proportion of the overall variability of a trait due to polygenic effects) of n-APC-SR was determined after adjustment for all clinical and laboratory variables, including factor V Leiden. Heritability coefficients (mean +/- standard deviation) were different for males (0.68 +/- 0.06) and females (0.34 +/- 0.12) younger than 25 years and in subjects older than 25 years: 0.37 +/- 0.09. This analysis provides strong evidence for a polygenic component influencing n-APC-SR in addition to factor V Leiden and suggests age- and gender-specific genetic effects.
authors.affiliation: Inserm ERIT-M 0323 - UHP Nancy 1, Vandoeuvre-lès-Nanacy, France.
authors.forename: Claudia
authors.initials: C
authors.lastname: Taralunga
authors.forename: René
authors.initials: R
authors.lastname: Gueguen
authors.forename: Sophie
authors.initials: S
authors.lastname: Visvikis
authors.forename: Véronique
authors.initials: V
authors.lastname: Regnault
authors.forename: Catherine
authors.initials: C
authors.lastname: Sass
authors.forename: Gérard
authors.initials: G
authors.lastname: Siest
authors.forename: Thomas
authors.initials: T
authors.lastname: Lecompte
authors.forename: Denis
authors.initials: D
authors.lastname: Wahl
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood / Q000209:etiology* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001779:Blood Coagulation Factors / Q000032:analysis; D001780:Blood Coagulation Tests; D002648:Child; D005165:Factor V / Q000235:genetics*; D005260:Female; D005783:Gender Identity; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011516:Prothrombin / Q000235:genetics*; D012044:Regression Analysis
chemical_list: D001779:Blood Coagulation Factors; D005165:Factor V; D011516:Prothrombin