VKORC1 gene polymorphisms and adverse events in Croatian patients on warfarin therapy

Abstract

The objective was to determine the impact of VKORC1 polymorphisms on warfarin anticoagulant therapy (stable warfarin maintenance dose, time required to reach therapeutic dose and time spent in therapeutic range) and its adverse events (overanticoagulation and bleeding events, time to first overanticoagulation or bleeding event, and therapy for bleeding events) in Croatian patients. Blood samples were collected from 186 patients on stable warfarin therapy. VKORC1 1173C>T and VKORC1 –1639G>A gene polymorphisms were analyzed using real-time PCR. Prothrombin time international normalized ratio (INR) values were determined and overanticoagulation as well as bleeding events were recorded. Both tested VKORC1 gene polymorphisms (VKORC1 1173C>T and VKORC1 -1639G>A) were in perfect linkage disequilibrium. Genotype analysis showed that 33.9% of patients were homozygous for wild-type, 46.8% were heterozygous and 19.4% were homozygous for the variant allele. We have found a statistically significant difference between variantallele carriers and wild-type patients in stable warfarin maintenance dose (p<0.001) and incidence of bleeding events (p=0.040). Patients homozygous for variant-allele were more likely to experience an overanticoagulation event in the first 30 days of therapy (p=0.040). Our study showed that VKORC1 1173C>T and VKORC1 -1639G>A gene polymorphisms are associated with stable warfarin maintenance dose and adverse events of warfarin therapy.