Warfarin therapy and pharmacogenetics: A narrative review of regional and Iraqi studies

Abstract

The aim of this work was to review several studies investigating the effects of genetic polymorphisms on warfarin dosing in regional and Iraqi studies and to report any consistent pattern of relevant findings. Despite the growing use of the recently introduced direct oral anticoagulants, warfarin is still the mainstay agent for oral anticoagulation because of its cost-effectiveness. However, a difficulty to establish a stable warfarin dose is frequently encountered. In addition to the warfarin narrow window of efficacy and safety, the main contributor to the challenging dosing is the wide range of variability in warfarin pharmacokinetics and pharmacodynamics among different patients as well as within the single patient context. A link between nonappropriateness of warfarin doses and dramatically increased risk of thromboembolic and hemorrhagic events has been well documented. Several single nucleotide polymorphisms (SNPs) in the genes implicated in warfarin pharmacokinetic and pharmacodynamic processes have been highlighted as possible contributors to warfarin dosing instability. Vitamin K epoxide reductase complex 1 gene SNPs have consistently been found to be the predominant genetic factor contributing the dosing variations. The SNP rs9923231 was significantly associated with the greatest predicting capability of warfarin dosage. However, a range of about 30%–50% of the variances in warfarin dosing was explained by the combined contribution effect of several genetic and nongenetic (clinical) factors in the regional and Iraqi studies.