OBJECTIVE: The objective of this study was to determine the influence of CYP2C9, VKORC1, CYP4F2, and GGCX genetic polymorphisms on mean daily dose of acenocoumarol in South Indian patients and to develop a new pharmacogenetic algorithm based on clinical and genetic factors. METHODS: Patients receiving acenocoumarol maintenance therapy (n = 230) were included in the study. Single nucleotide polymorphisms (SNP) of CYP2C9, VKORC1, CYP4F2, and GGCX were genotyped by real-time polymerase chain reaction (RT-PCR) method. RESULTS: The mean daily acenocoumarol maintenance dose was found to be 3.7 ± 2.3 (SD) mg/day. The CYP2C9 *1*2, CYP2C9 *1*3, and CYP2C9 *2*3 variant genotypes significantly reduced the dose by 56.7 % (2.0 mg), 67.6 % (1.6 mg), and 70.3 % (1.5 mg) than wild-type carriers 4.1 mg, p < 0.0001. The genetic variants of CYP2C9 and GGCX (rs11676382) were found to be associated with lower acenocoumarol dose, whereas CYP4F2 (rs2108622) was associated with higher doses. Age, body mass index (BMI), variation of CYP2C9, VKORC1, CYP4F2, and GGCX were the major determinants of acenocoumarol maintenance dose, accounting for 61.8 % of its variability (adjusted r (2) = 0.615, p < 0.0001). Among the VKORC1 variants, rs9923231 alone contributed up to 28.6 % of the acenocoumarol dose variation. CONCLUSION: VKORC1 rs9923231 polymorphism had the highest impact on acenocoumarol daily dose. A new pharmacogenetic algorithm was established to determine the acenocoumarol dose in South Indian population.
OBJECTIVE: The objective of this study was to determine the influence of CYP2C9, VKORC1, CYP4F2, and GGCX genetic polymorphisms on mean daily dose of acenocoumarol in South Indian patients and to develop a new pharmacogenetic algorithm based on clinical and genetic factors. METHODS:Patients receiving acenocoumarol maintenance therapy (n = 230) were included in the study. Single nucleotide polymorphisms (SNP) of CYP2C9, VKORC1, CYP4F2, and GGCX were genotyped by real-time polymerase chain reaction (RT-PCR) method. RESULTS: The mean daily acenocoumarol maintenance dose was found to be 3.7 ± 2.3 (SD) mg/day. The CYP2C9 *1*2, CYP2C9 *1*3, and CYP2C9 *2*3 variant genotypes significantly reduced the dose by 56.7 % (2.0 mg), 67.6 % (1.6 mg), and 70.3 % (1.5 mg) than wild-type carriers 4.1 mg, p < 0.0001. The genetic variants of CYP2C9 and GGCX (rs11676382) were found to be associated with lower acenocoumarol dose, whereas CYP4F2 (rs2108622) was associated with higher doses. Age, body mass index (BMI), variation of CYP2C9, VKORC1, CYP4F2, and GGCX were the major determinants of acenocoumarol maintenance dose, accounting for 61.8 % of its variability (adjusted r (2) = 0.615, p < 0.0001). Among the VKORC1 variants, rs9923231 alone contributed up to 28.6 % of the acenocoumarol dose variation. CONCLUSION:VKORC1rs9923231 polymorphism had the highest impact on acenocoumarol daily dose. A new pharmacogenetic algorithm was established to determine the acenocoumarol dose in South Indian population.
Authors: R M F van Schie; A M V Babajeff; T Schalekamp; J A M Wessels; S le Cessie; A de Boer; F J M van der Meer; E van Meegen; T I Verhoef; F R Rosendaal; A H Maitland-van der Zee Journal: J Thromb Haemost Date: 2012-05 Impact factor: 5.824
Authors: Daniel E Singer; Gregory W Albers; James E Dalen; Alan S Go; Jonathan L Halperin; Warren J Manning Journal: Chest Date: 2004-09 Impact factor: 9.410
Authors: Cristina Lucía Dávila-Fajardo; Xando Díaz-Villamarín; Alba Antúnez-Rodríguez; Ana Estefanía Fernández-Gómez; Paloma García-Navas; Luis Javier Martínez-González; José Augusto Dávila-Fajardo; José Cabeza Barrera Journal: Genes (Basel) Date: 2019-04-01 Impact factor: 4.096
Authors: Hoi Y Tong; Cristina Lucía Dávila-Fajardo; Alberto M Borobia; Luis Javier Martínez-González; Rubin Lubomirov; Laura María Perea León; María J Blanco Bañares; Xando Díaz-Villamarín; Carmen Fernández-Capitán; José Cabeza Barrera; Antonio J Carcas Journal: PLoS One Date: 2016-03-15 Impact factor: 3.240