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Abstract
haemostasis is aprotective processes that has evolved in order to maintain astable physology. the haemostatic system is acomplex mosaic of activating or inhibitory feedback or feed-forward pathways, integrating its five magor components (blood vessels,platelets,coagulation factors, coagulation inhibitors and fibrinolytic elements.
Genotype based modelling explained a large amount of dose-variations compared with those associated with clinical variables alone, and with non-genetic predictors as age and body weight (Tong and Toshiyuki, 2007).
Besides up to the two-thirds of the inter-individual variability in warfarin dosage requirements is explained by CYP2C9 and VKORC1 genotypes, together with environmental factors, the weak association found between warfarin sensitivity and polymorphisms in other genes could explain up to a 10% additional dose variance (Wadelius et al., 2005).
There appears to be little contribution from genes that encode for clotting factors, (Shikata et al., 2004) γ-glutamyl carboxylase (GGCX), (Kimura et al., 2007) calumenin, (Gonzales-Conejero et al., 2007) microsomal epoxide hydrolase (mEH), (Loebstein et al., 2005) apolipoprotein E (ApoE) (Visser et al., 2005) and multidrug resistance 1 (MDR1) (Wadelius et al., 2004).
As a perspective, it appears appropriate to increase the number of candidate genes involved in the metabolism of warfarin to set up a powerful tool, easy for a rapid use into all laboratories and clinical settings, to improve the warfarin therapy management. However, it will require to be validated, and ethical/legal/social implication associated with genetic testing considered, before to be introduced into clinical practice.