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Does the genotype predict the phenotype? Evaluations of the hemostatic proteome
Author(s) -
Mann K. G.,
BrummelZiedins K.,
Undas A.,
Butenas S.
Publication year - 2004
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2004.00958.x
Subject(s) - proteome , phenotype , coagulation , population , thrombin , genetic heterogeneity , bioinformatics , medicine , proteomics , computational biology , immunology , biology , genetics , platelet , gene , environmental health
Summary. In this review, the complexity arising from the heterogeneity of the human hemostatic proteome is introduced and discussed with respect to impact on the diagnosis, prophylaxis and therapeutic interventions in thrombotic and hemorrhagic diseases. In the ‘healthy’ population, coagulation factor levels extend over a 2–4‐fold range in concentration. In addition, the qualitative performance of these proteins is governed by many molecular events which are influenced both by genetic instructions which influence post‐translational modification and by environmental processes that alter coagulation proteins during circulation. As a consequence, the stimulus–response coupling which follows tissue factor presentation to blood and the subsequent expression of thrombin activity is highly variable even in the ‘normal’ population. The consequences of this molecular heterogeneity and its potential influence on the diagnosis, prophylaxis and ultimate therapy of coagulation diseases are illustrated. It is the intention of the authors to be provocative; encouraging further investigations to understand the clinical significance of the heterogeneity of the human hemostatic proteome.