Effect of <i>VKORC1, CYP2C9</i> and <i>CYP4F2</i> Genetic Variants in Early Outcomes During Acenocoumarol Treatment

Juan José Cerezo-Manchado, Vanessa Roldán, Mario Rosafalco, Ana Isabel Antón, Ana B. Arroyo, Nuria García‐Barberá, Ana Belén Olivares Martínez, José Padilla, Javier Corral, Vicente Vicente,

Pharmacogenomics · 2014 · 10 citations · 19 references

Concepts

Abstract

AIM: To analyze VKORC1, CYP2C9 and CYP4F2 polymorphisms in relation to the main outcomes in the first stages of acenocoumarol therapy. PATIENTS & METHODS: Nine hundred and forty one patients who had started therapy and in whom time to stable dosage, time to over-anticoagulation and adverse events occurred during 3 first months were retrospectively analyzed. RESULTS: VKORC1 AA patients needed fewer days to reach stable dosage (p = 0.017). International normalized ratio [INR] at 72 h, and VKORC1 and CYP2C9 genotypes conditioned INR values >2.5 (p < 0.001, p = 0.002 and p < 0.001, respectively), whereas CYP4F2 T carriers had a low risk of the same outcome (p = 0.009). In regards to combined genotypes, CYP4F2 had a significant effect on over-anticoagulation at the beginning of therapy except for the VKORC1 AA and CYP2C9*3 combination. CONCLUSION: In addition to VKORC1 and CYP2C9, CYP4F2 gene has a slight but significant role in reaching INR >2.5 during the first weeks of acenocoumarol therapy.

References

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