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Phenotypic sensitivity to activated protein C in healthy families: importance of genetic components and environmental factors
Author(s) -
Taralunga Claudia,
Gueguen René,
Visvikis Sophie,
Regnault Véronique,
Sass Catherine,
Siest Gérard,
Lecompte Thomas,
Wahl Denis
Publication year - 2004
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2004.05055.x
Subject(s) - heritability , factor v leiden , protein c , antithrombin , medicine , genetics , biology , offspring , gene–environment interaction , trait , factor v , endocrinology , gene , genotype , pregnancy , venous thrombosis , computer science , programming language , heparin , thrombosis
Summary 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.