The impact of the CYP2C9 and VKORC1 polymorphisms on acenocoumarol dose requirements in a Romanian population

Buzoianu, Anca Dana; Militaru, Florentina Claudia; Vesa, Ștefan Cristian; Crişan, Sorin

doi:10.1016/j.bcmd.2012.10.010

Cited by 12 publications

(8 citation statements)

References 22 publications

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“…Other studies also demonstrated the influence of age on the dosage of acenocoumarol, but the mechanism of this association has not been fully elucidated yet. [8,[30][31][32][33].…”

Section: Discussionmentioning

confidence: 99%

“…The combination of two polymorphisms in CYP2C9 and VKORC1 could explain between 25 and 40% (20-25% for VKORC1 and 5-15% for CYP2C9) of the variability in therapeutic doses of coumarins as acenocoumarol [15,16], whereas the combination of demographic, clinical and genetic factors explains 45-55% of the total variation in the optimal therapeutic dose [1,8,[17][18][19][20][21][22].…”

Section: Aim and Methodsmentioning

confidence: 99%

“…[5]. Genetic factors also strongly correlate with the dose of acenocoumarol in Caucasians [1,[6][7][8][9]. The pharmacokinetics and pharmacodynamics of this drug are affected by functional polymorphisms in both CYP2C9 and VKORC1 genes [10,11].…”

mentioning

confidence: 99%

“…The pharmacokinetics and pharmacodynamics of this drug are affected by functional polymorphisms in both CYP2C9 and VKORC1 genes [10,11]. The polymorphic variants in both genes independently correlate with the clinical dose of acenocoumarol [12] and the time required to achieve an effective dose for stable anticoagulation [12][13][14].The combination of two polymorphisms in CYP2C9 and VKORC1 could explain between 25 and 40% (20-25% for VKORC1 and 5-15% for CYP2C9) of the variability in therapeutic doses of coumarins as acenocoumarol [15,16], whereas the combination of demographic, clinical and genetic factors explains 45-55% of the total variation in the optimal therapeutic dose [1,8,[17][18][19][20][21][22].There are several pharmacogenetic models found in the literature for predicting the optimal warfarin dose for various population groups. However, there are limited papers on optimal acenocoumarol dose.…”

mentioning

confidence: 99%

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Estimation and Validation of Acenocoumarol Dosing Algorithms In Bulgarian Patients with Cardiovascular Diseases

Tzveova

Dimitrova-Karamfilova²,

Saraeva

et al. 2015

Per. Med.

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“…Other studies also demonstrated the influence of age on the dosage of acenocoumarol, but the mechanism of this association has not been fully elucidated yet. [8,[30][31][32][33].…”

Section: Discussionmentioning

confidence: 99%

Section: Aim and Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Estimation and Validation of Acenocoumarol Dosing Algorithms In Bulgarian Patients with Cardiovascular Diseases

Tzveova

Dimitrova-Karamfilova²,

Saraeva

et al. 2015

Per. Med.

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“…DNA extraction was performed using a genomic DNA purification kit (Wizard Genomic DNA Purification Kit, Promega, Madison, WI, USA). Genotyping of the VKORC1 [24][25][26], CYP4F2 [27], and GGCX [27] polymorphisms was performed as previously described. VKORC1 and CYP4F2 mutational status was dichotomized between no mutation and either monoallelic or biallelic mutation.…”

Section: Methodsmentioning

confidence: 99%

CYP4F2 and VKORC1 Polymorphisms Amplify the Risk of Carotid Plaque Formation

Vesa

Vlaicu

Văcăraș

et al. 2020

Genes

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Introduction: Atherosclerosis represents the process by which fibrous plaques are formed in the arterial wall, increasing its rigidity with a subsequent decrease in blood flow which can lead to several cardiovascular events. Seeing as vitamin K antagonists are involved in the pathogenesis of atherosclerosis, we decided to investigate whether polymorphisms in genes that influence vitamin K metabolism might have an impact in modulating the risk of plaque formation. Patients and Methods: In the current study we included adult patients admitted in the Clinical Municipal Hospital of Cluj-Napoca without any carotid or femoral plaques clinically visible at the initial investigation, and a five year follow-up was subsequently performed. We recorded the following patient characteristics: age at inclusion, gender, area of living, smoking, presence of carotid and/or femoral plaques at five years, ischemic heart disease, arterial hypertension, atrial fibrillation, heart failure, diabetes mellitus, obesity, dyslipidemia, drug (oral anticoagulants, antihypertensives, hypolipidemic, anti-diabetic) use and status for the following gene polymorphisms: VKORC1 1639 G>A, CYP4F2 1347 G>T and GGCX 12970 C>G. Results: We observed that the major predictor of both carotid and femoral plaque formation is represented by ischemic cardiac disease. VKORC1 and CYP4F2 polymorphisms did not predict plaque formation, except for VKORC1 homozygous mutants. Nonetheless, both VKORC1 and CYP4F2 interacted with ischemic cardiac disease, increasing the risk of developing a carotid plaque, while only CYP4F2, but not VKORC1, interacted with ischemic cardiac disease to increase the risk of femoral plaque formation. Conclusions: We documented that CYP4F2 and VKORC1 polymorphisms boost the proinflammatory plaque environment (observed indirectly through the presence of ischemic heart disease), increasing the risk of plaque development.

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Influence of genetic and non-genetic factors on acenocoumarol maintenance dose requirement in a Tunisian population

Ajmi

Omezzine

Achour

et al. 2018

Eur J Clin Pharmacol

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The impact of the CYP2C9 and VKORC1 polymorphisms on acenocoumarol dose requirements in a Romanian population

Cited by 12 publications

References 22 publications

Estimation and Validation of Acenocoumarol Dosing Algorithms In Bulgarian Patients with Cardiovascular Diseases

Estimation and Validation of Acenocoumarol Dosing Algorithms In Bulgarian Patients with Cardiovascular Diseases

CYP4F2 and VKORC1 Polymorphisms Amplify the Risk of Carotid Plaque Formation

Influence of genetic and non-genetic factors on acenocoumarol maintenance dose requirement in a Tunisian population

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