The c.-1639G gt A polymorphism of the VKORC1 gene in Serbian population: retrospective study of the variability in response to oral anticoagulant therapy
Само за регистроване кориснике
2010
Чланак у часопису (Објављена верзија)
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Метаподаци
Приказ свих података о документуАпстракт
A single nucleotide polymorphism c.-1639G gt 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 gt 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 lt 0.0001). Carriers of AA genotype were more likely to be overanticoagulated during follow-up a...fter initiation of VKA when compared with carriers of the GA and GG genotypes (P lt 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 lt 0.0001). VKORC1 c.-1639G gt 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. Blood Coagul Fibrinolysis 21:558-563
Кључне речи:
VKORC1 / variability in response to VKA / c.-1639 G gt A polymorphism / acenocoumarol doseИзвор:
Blood Coagulation & Fibrinolysis, 2010, 21, 6, 558-563Издавач:
- Lippincott Williams & Wilkins, Philadelphia
Финансирање / пројекти:
- Структурални елементи генома у модулацији фенотипа (RS-MESTD-MPN2006-2010-143051)
DOI: 10.1097/MBC.0b013e32833c2988
ISSN: 0957-5235
PubMed: 20581661
WoS: 000281115200009
Scopus: 2-s2.0-77955925926
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Kovač, Mirjana AU - Maslac, Aleksandar R. AU - Rakićević, Ljiljana AU - Radojković, Dragica PY - 2010 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/451 AB - A single nucleotide polymorphism c.-1639G gt 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 gt 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 lt 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 lt 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 lt 0.0001). VKORC1 c.-1639G gt 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. Blood Coagul Fibrinolysis 21:558-563 PB - Lippincott Williams & Wilkins, Philadelphia T2 - Blood Coagulation & Fibrinolysis T1 - The c.-1639G gt A polymorphism of the VKORC1 gene in Serbian population: retrospective study of the variability in response to oral anticoagulant therapy EP - 563 IS - 6 SP - 558 VL - 21 DO - 10.1097/MBC.0b013e32833c2988 ER -
@article{ author = "Kovač, Mirjana and Maslac, Aleksandar R. and Rakićević, Ljiljana and Radojković, Dragica ", year = "2010", abstract = "A single nucleotide polymorphism c.-1639G gt 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 gt 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 lt 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 lt 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 lt 0.0001). VKORC1 c.-1639G gt 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. Blood Coagul Fibrinolysis 21:558-563", publisher = "Lippincott Williams & Wilkins, Philadelphia", journal = "Blood Coagulation & Fibrinolysis", title = "The c.-1639G gt A polymorphism of the VKORC1 gene in Serbian population: retrospective study of the variability in response to oral anticoagulant therapy", pages = "563-558", number = "6", volume = "21", doi = "10.1097/MBC.0b013e32833c2988" }
Kovač, M., Maslac, A. R., Rakićević, L.,& Radojković, D.. (2010). The c.-1639G gt A polymorphism of the VKORC1 gene in Serbian population: retrospective study of the variability in response to oral anticoagulant therapy. in Blood Coagulation & Fibrinolysis Lippincott Williams & Wilkins, Philadelphia., 21(6), 558-563. https://doi.org/10.1097/MBC.0b013e32833c2988
Kovač M, Maslac AR, Rakićević L, Radojković D. The c.-1639G gt A polymorphism of the VKORC1 gene in Serbian population: retrospective study of the variability in response to oral anticoagulant therapy. in Blood Coagulation & Fibrinolysis. 2010;21(6):558-563. doi:10.1097/MBC.0b013e32833c2988 .
Kovač, Mirjana, Maslac, Aleksandar R., Rakićević, Ljiljana, Radojković, Dragica , "The c.-1639G gt A polymorphism of the VKORC1 gene in Serbian population: retrospective study of the variability in response to oral anticoagulant therapy" in Blood Coagulation & Fibrinolysis, 21, no. 6 (2010):558-563, https://doi.org/10.1097/MBC.0b013e32833c2988 . .