Souto JC, Almasy L, Borrell M, Blanco-Vaca F, Mateo J, Soria JM, et al.
Am J Hum Genet. 2000;67(6):1452-1459
Although there are a number of well-characterized genetic defects that lead to increased risk of thrombosis, little information is available on the relative importance of genetic factors in thrombosis risk in the general population. We performed a family-based study of the genetics of thrombosis in the Spanish population to assess the heritability of thrombosis and to identify the joint actions of genes on thrombosis risk and related quantitative hemostasis phenotypes. We examined 398 individuals in 21 extended pedigrees. Twelve pedigrees were ascertained through a proband with idiopathic thrombosis, and the remaining pedigrees were randomly ascertained. The heritability of thrombosis liability and the genetic correlations between thrombosis and each of the quantitative risk factors were estimated by means of a novel variance component method that used a multivariate threshold model. More than 60% of the variation in susceptibility to common thrombosis is attributable to genetic factors. Several quantitative risk factors exhibited significant genetic correlations with thrombosis, indicating that some of the genes that influence quantitative variation in these physiological correlates also influence the risk of thrombosis. Traits that exhibited significant genetic correlations with thrombosis included levels of several coagulation factors (factors VII, VIII, IX, XI, XII, and von Willebrand), tissue plasminogen activator, homocysteine, and the activated protein C ratio. This is the first study that quantifies the genetic component of susceptibility to common thrombosis. The high heritability of thrombosis risk and the significant genetic correlations between thrombosis and related risk factors suggest that the exploitation of correlated quantitative phenotypes will aid the search for susceptibility genes.
Comentario del Dr. Ramón Lecumberri
A partir de la descripción en 1994 del factor V Leiden y en 1996 del polimorfismo G20210A de la protrombina, asistimos a la publicación de multitud de estudios que trataban de identificar nuevas alteraciones trombofílicas con un impacto significativo en el riesgo de trombosis venosa o arterial. Básicamente, se distinguían dos aproximaciones metodológicas: estudios de casos-control y estudios de agrupación familiar. Entre estos últimos, destacó el proyecto GAIT, liderado por el grupo de trombosis del Hospital Sant Pau de Barcelona.
En este interesante estudio, los autores evaluaron mediante estadística genética el porcentaje de la heredabilidad de la trombosis atribuible a factores genéticos, estimándose en un 60%.
Si el FV Leiden y la protrombina G20210A están presentes en, aproximadamente, el 30% de los pacientes con TEV y la deficiencia de anticoagulante no llega al 5%, debían existir otros factores aún no identificados.
Sin embargo, hasta la fecha, si exceptuamos el grupo sanguíneo, ningún polimorfismo aislado ha demotrado tener una impotancia significativa de forma aislada, lo que refuerza el mensaje de que la ETEV debe ser considerada una enfermedad compleja, de carácter multigénico.
