PREVALENCE OF THE VKORC1 -1639 G>A MUTATION INVOLVED IN VARIABILITY OF DRUG RESPONSE TO VITAMIN K ANTAGONISTS

Abstract

Vitamin K Antagonists (VKA) account for one-third of the anticoagulants present, and are used in order to prevent and treat different thrombotic disorders such as atrial fibrillation and deep venous thrombosis. However, many polymorphisms in genes affecting pharmacokinetic and pharmacodynamic properties of VKAs have been shown to affect dose requirements of these drugs. In our study, we genotyped 28 Moroccan individuals, for the VKORC1 ' 1639 G>A polymorphism using the RFLP technique. This technique relies on enzymatic restriction to determine the presence or absence of the three genotypic profiles: wild type (GG), mutant heterozygote (GA), and mutant homozygote (AA). The identification of these profiles depends on whether the restriction occurs at the specific site. Our aim was to evaluate the prevalence of this polymorphism in our population. This evaluation would help the orientation and tailoring of VKAs treatment based on what polymorphisms are present in each individual. In case an individual carries the mutant allele, an adjustment to lower doses would be necessary, to prevent unwanted adverse reactions, like excessive bleeding. Therefore, our study contributes to the field of personalized medicine, where treatments are optimized based on the genetic makeup of each individual, as well as the field of pharmacogenetics, which studies the effects of genetic variations on drug response.