ORIGINAL ARTICLESThe c.-1639G>A polymorphism of the VKORC1 gene in Serbian population: retrospective study of the variability in response to oral anticoagulant therapyKovac, Mirjana Ka; Maslac, Aleksandar Ra; Rakicevic, Ljiljana Bb; Radojkovic, Dragica PbAuthor Information aBlood Transfusion Institute of Serbia, Svetog Save 39a, Serbia bInstitute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, Belgrade, Serbia Received 2 February, 2009 Revised 20 April, 2010 Accepted 27 April, 2010 Correspondence to Ljiljana Rakicevic, Institute of Molecular Genetics and Genetic Engineering, Vojvode Stepe 444a, P.O. Box 23, 11010 Belgrade, Serbia E-mail: firstname.lastname@example.org Blood Coagulation & Fibrinolysis: September 2010 - Volume 21 - Issue 6 - p 558-563 doi: 10.1097/MBC.0b013e32833c2988 Buy Metrics Abstract A single nucleotide polymorphism c.-1639G>A in the promoter region of vitamin K-epoxide reductase (VKORC1) gene has been found to account for most of the variability in response to oral vitamin K antagonist (VKA). Our aim was to study the effect of c.-1639G>A polymorphism on the acenocoumarol dosage requirements in a group of patients under stable anticoagulation, and to estimate the variability in response to VKA. We conducted a retrospective cohort analysis of 200 stable anticoagulation patients followed from the initiation of VKA. Out of 43 low-dose patients, 40 (93%) carried the A allele. The A allele was less frequent in the group of 30 patients requiring high VKA dose; among these patients 13 (43.3%) carried the A allele in the heterozygous form and none of them carried AA genotype. Patients with GG genotype required 2.6 times higher dose than patients carriers of AA genotype (P < 0.0001). Carriers of AA genotype were more likely to be overanticoagulated during follow-up after initiation of VKA when compared with carriers of the GA and GG genotypes (P < 0.0001). Patients with GG genotype spent more time below therapeutic range compared with patients carriers of AA (P = 0.0328) and GA genotype (P < 0.0001). VKORC1 c.-1639G>A polymorphism significantly influenced VKA dose and represented a good predictor of individuals predisposed to unstable anticoagulation. Pharmacogenetic testing could predict a high risk of overdose among 28.5% of our patients, carriers of AA genotype, before the initiation of anticoagulation. © 2010 Lippincott Williams & Wilkins, Inc.