Genetic determinants of hemostasis phenotypes in Spanish families
Genetic determinants of hemostasis phenotypes in Spanish families
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DOI：
10.1161/01.cir.101.13.1546
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发表时间：
2000-04-04
期刊：
影响因子：
37.8
通讯作者：
Fontcuberta, J
中科院分区：
文献类型：
--
作者：
Souto, JC;Almasy, L;Fontcuberta, J
背景-最近的研究描述了由于蛋白C、蛋白S和活化蛋白C抵抗比等止血参数水平异常而影响血栓形成风险的基因突变。虽然这些突变表明基因在决定某些止血相关表型的变异性中起作用，但尚未评估遗传影响对这些性状的相对重要性。方法和结果-在21个扩展家系的397个个体样本中，评估了遗传和环境影响对一组止血相关表型的相对贡献。测量的协变量(性别、年龄、吸烟和外源性性激素)、基因和家庭成员共有的环境变量对27项止血相关指标的影响进行了量化。所有这些表型都表现出显著的遗传贡献，经协变量效应校正后，大多数遗传力在残留表型方差的22%到55%之间。活化蛋白C抵抗比、活化部分凝血活酶时间和凝血因子XII的遗传力最强，分别有71.3%、83.0%和67.3%的残余表型变异可归因于遗传效应。结论--这些结果清楚地表明了遗传因素在决定止血相关表型变异中的重要性，这些表型是凝血和纤溶途径的组成部分，与血栓形成的风险有关。如此强大的遗传效应的存在表明，有可能定位以前未知的基因，这些基因影响这些止血相关表型的数量变异，这些表型可能导致血栓形成的风险。
Background-Recent studies have described genetic mutations that affect the risk of thrombosis as a result of abnormal levels of such hemostatic parameters as protein C, protein S, and the activated protein C resistance ratio. Although these mutations suggest that genes play a part in determining variability in some hemostasis-related phenotypes, the relative importance of genetic influences on these traits has not been evaluated.Methods and Results-The relative contributions of genetic and environmental influences to a panel of hemostasis-related phenotypes were assessed in a sample of 397 individuals in 21 extended pedigrees. The effects of measured covariates (sex, age, smoking, and exogenous sex hormones), genes, and environmental variables shared by members of a household were quantified for 27 hemostasis-related measures. All of these phenotypes showed significant genetic contributions, with the majority of heritabilities ranging between 22% and 55% of the residual phenotypic variance after correction for covariate effects. Activated protein C resistance ratio, activated partial thromboplastin time, and Factor XII showed the strongest heritabilities, with 71.3%, 83.0%, and 67.3%, respectively, of the residual phenotypic variation attributable to genetic effects.Conclusions-These results clearly demonstrate the importance of genetic factors in determining variation in hemostasis-related phenotypes that are components of the coagulation and fibrinolysis pathways and that have been implicated in risk for thrombosis. The presence of such strong genetic effects suggests that it will be possible to localize previously unknown genes that influence quantitative variation in these hemostasis-related phenotypes that may contribute to risk for thrombosis.