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Pharmacogenetic Aspects of Coumarinic Oral Anticoagulant Therapies

Authors
  • Rathore, Saurabh Singh1
  • Agarwal, Surendra Kumar2
  • Pande, Shantanu2
  • Singh, Sushil Kumar3
  • Mittal, Tulika1
  • Mittal, Balraj1
  • 1 Sanjay Gandhi Post Graduate Institute of Medical Sciences, Department of Genetics, Lucknow, 226014, India , Lucknow (India)
  • 2 Sanjay Gandhi Post Graduate Institute of Medical Sciences, Cardio-Vascular & Thoracic Surgery, Lucknow, India , Lucknow (India)
  • 3 Chhatrapati Shahuji Maharaj Medical University (Erstwhile King George’s Medical University), Thoracic & Cardio-Vascular Surgery, Lucknow, India , Lucknow (India)
Type
Published Article
Journal
Indian Journal of Clinical Biochemistry
Publisher
Springer-Verlag
Publication Date
May 01, 2011
Volume
26
Issue
3
Pages
222–229
Identifiers
DOI: 10.1007/s12291-011-0133-3
Source
Springer Nature
Keywords
License
Yellow

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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