Pharmacogenetics of acenocoumarol: CYP2C9 *2 and VKORC1 c.-1639G&gt;A, 497C&gt;G, 1173C&gt;T, and 3730G&gt;A variants influence drug dose in anticoagulated patients

Verde, Zoraida; Santiago, Catalina; Valle, Beatriz; Fernández-Santander, Ana; Bandrés, Fernando; Calvo, E.; Ruiz, Jonatan R.; Gallego, Félix Gómez; Lucía, Alejandro

doi:10.1160/th08-09-0578

Cited by 8 publications

(9 citation statements)

References 19 publications

(34 reference statements)

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“…The group comparisons of genotypic and allelic frequency of these polymorphisms have been published elsewhere [2].Values of GS: 0 = very slow metaboliser (low dose), 1 = slow metaboliser (medium dose), and 2 = normal metaboliser (high dose).…”

Section: Resultsmentioning

confidence: 99%

“…The group comparisons of genotypic and allelic frequency of these polymorphisms have been published elsewhere [2].…”

Section: Resultsmentioning

confidence: 99%

“…target INR of 3.0–4.0 in patients with a prosthetic heart valve and of 2.0–3.0 for the rest of patients. They were free of any concomitant severe disease known to interfere with acenocoumarol treatment [2].…”

Section: Methodsmentioning

confidence: 99%

“…The identification of the genes encoding cytochrome P-450 2C9 enzyme ( CYP2C9 ), the principal metabolizing enzyme of the coumarins, and vitamin K epoxide reductase enzyme ( VKORC1 ), the molecular target for coumarins, has strongly stimulated the research on pharmacogenetics of coumarins in the last decade. Several variants in CYP2C9 (CYP2C9 *2 and especially the CYP2C9 *3 allele) and VKORC1 genes (especially the 1639G>A polymorphism) are associated with effective coumarin derivative dose [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]. CYP2C9 and VKORC1 seem the only genes with relevant effects on coumarin response [10], except the rs2108622 polymorphism in the gene encoding cytochrome P450, family 4, subfamily F, polypeptide 2 ( CYP4F2 ) which could also influence warfarin dose [9].…”

Section: Introductionmentioning

confidence: 99%

“…We chose the aforementioned gene variants based on their high frequency among Caucasians [13] and on previous research showing their association with acenocoumarol dose [2]. Briefly, the risk of requiring a low dose of acenocoumarol is significantly higher in patients carrying at least one CYP2C9 *3 allele, and the KVORC1 genotypes c.-1639 AA, 497 CG and GG, and 1173 TT [2].…”

Section: Introductionmentioning

confidence: 99%

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A Novel, Single Algorithm Approach to Predict Acenocoumarol Dose Based on CYP2C9 and VKORC1 Allele Variants

et al. 2010

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The identification of CYP2C9 and VKORC1 genes has strongly stimulated the research on pharmacogenetics of coumarins in the last decade. We assessed the combined influence of CYP2C9 *2 and *3, and VKORC1 c.-1639G>A, 497C>G, and 1173C>T variants, on acenocoumarol dosage using a novel algorithm approach, in 193 outpatients who had achieved stable anticoagulation. We constructed an “acenocoumarol-dose genotype score” (AGS, maximum score = 100) based on the number of alleles associated with higher acenocoumarol dosage carried by each subject for each polymorphism. The mean AGS was higher in the high-dose (>28mg/week) compared with the low-dose (<7mg/week) group (mean(SEM) of 84.1±3.4 vs. 62.2±4.8, P = 0.008). An AGS>70 was associated with an increased odds ratio (OR) of requiring high acenocoumarol dosage (OR: 3.347; 95%CI: 1.112–10.075; P = 0.032). In summary, although more research is necessary in other patient cohorts, and this algorithm should be replicated in an independent sample, our data suggest that the AGS algorithm could be used to help discriminating patients requiring high acenocoumarol doses to achieve stable anti-coagulation.

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Section: Resultsmentioning

confidence: 99%

“…The group comparisons of genotypic and allelic frequency of these polymorphisms have been published elsewhere [2].…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%