Pharmacogenetic Aspects of Coumarinic Oral Anticoagulant Therapies |
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| Authors: | Saurabh Singh Rathore Surendra Kumar Agarwal Shantanu Pande Sushil Kumar Singh Tulika Mittal Balraj Mittal |
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| Institution: | (1) Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226014, India;(2) Cardio-Vascular & Thoracic Surgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India;(3) Thoracic & Cardio-Vascular Surgery, Chhatrapati Shahuji Maharaj Medical University (Erstwhile King George’s Medical University), Lucknow, India; |
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| Abstract: | Coumarinic oral-anticoagulants (COAs) are commonly used for treatment of thromboembolic events. However, these medications
have a narrow therapeutic range and there are large inter-individual variations in drug response. This is especially important
in the initial phases of oral-anticoagulant therapy. Recent advancements in pharmacogenetics have established that clinical
outcomes in oral-anticoagulant therapy are affected by genetic factors. The allelic variants of genes like cytochrome P450
2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) are closely associated with maintenance dose of oral
anti-coagulants. In addition, GGCX (Gamma-glutamyl carboxylase) polymorphism at position 12970 (rs11676382), CYP4F2 (rs2108622;
V433M; 1347 C > T) and Apolipoprotein E (APOE) variants have been shown to explain a small but significant influence on dose
requirements. There are large differences in the frequencies of these polymorphisms between different world populations which
are also related to the requirements of oral anticoagulants. However, the final drug dosage in an individual is determined
by complex sets of genetic and environmental factors and several dosing algorithms which combine clinical and genetic parameters
to predict therapeutic COA doses have also been developed. The algorithm based dose prediction shows the importance of pharmacogenetic
testing in patients undergoing oral anticoagulant therapies. |
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| Keywords: | Coumarinic oral anticoagulants Pharmacogenetics Vitamin K cycle Drug metabolism Polymorphism Dosing algorithm |
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