INVESTIGATING THE GENETIC EFFECT OF VKORC1 GENE POLYMORPHISM ON WARFARIN RESPONSE IN EGYPTIAN HEART PATIENTS

Abstract

Warfarin is a common oral anticoagulant, but the dose needed for each patient can vary by as much as 20 times due to both environmental and genetic factors. Some of the most important genetic targets of warfarin include the vitamin K epoxide reductase complex 1 (VKORC1) gene. This study investigated the genetic effect of the VKORC1 gene on warfarin response using real-time PCR in a total of 100 warfarin-treated Egyptian heart patients and 40 controls. This study confirmed a genetic association of the VKORC1 SNP rs9934438 with warfarin response. The VKORC1 SNP analysis identified the presence of 26% homozygous variant (A/A), 42% heterozygous variant (A/G), and 32% wild-type variant (G/G) among patients compared to 20%, 25%, and 55% of controls. A significant difference was found between VKORC1 genotype allelic distribution in study patients and controls (P<0.05). Patients carriers of the VKORC1 genotype (A/G) required a lower daily warfarin dose than the other variants (P=0.006). The total number of patients who reached the optimal therapeutic goal of warfarin dose of 100 study patients was 19 compared to 81 ones who did not. Females required lower daily warfarin doses than males. VKORC1 gene polymorphism did not affect INR outcomes, but it was associated with a decrease in warfarin response. The VKORC1 gene polymorphism could explain the interindividual variation in warfarin response among Egyptian patients. Our findings suggest that dosing algorithms incorporating the genetic elements of the VKORC1 genotype are essential to determine warfarin dose and could optimize the therapeutic effectiveness of warfarin and minimize its adverse effects.