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• W2034506206 abstract "Introduction VKORC1 and cytochrome CYP2C9 genetic variants contribute largely to inter-individual variations in vitamin K antagonists (VKAs) dose requirements. Cytochrome P450 4 F2 isoform (CYP4F2), gamma-glutamyl carboxylase (GGCX) and apolipoprotein E (APOE) polymorphisms have been suggested to be of minor significance. Materials and Methods We sought to assess the impact of those polymorphisms on dose requirements in Central-Eastern European cohort of 479 patients receiving acenocoumarol (n = 260) or warfarin (n = 219). Results There were no differences between the acenocoumarol and warfarin groups with regard to the gender, age, body mass index and international normalized ratio. The VKORC1 c.-1639A allele carriers required a lower dose of acenocoumarol and warfarin than the non-carriers (28.0 [21.0–35.0] vs. 42.0 [28.0–56.0] mg/week, p < 0.0001; 35.0 [28.0–52.0] vs. 52.0 [35.0–70.0] mg/week, p = 0.0001, respectively). Carriers of *2 and/or *3 variant alleles for CYP2C9 also required a lower dose of warfarin as compared with *1*1 carriers (35.0 [31.5–52.5] vs. 43.8 [35.0–60.2] mg/week, p = 0.02; 35.0 [23.5–35.0] vs. 43.8 [35.0-60.2] mg/week, p < 0.0001, respectively). Similarly, possession of G allele of GGCX c.2084 + 45 polymorphism was associated with lower warfarin dose (35.0 [26.3–39.2] vs. 45.5 [35.0–65.1] mg/week, p = 0.03). No effect of CYP2C9*2,-*3 and GGCX c.2084 + 45G > C polymorphisms on acenocoumarol dosage was observed. Interestingly, carriers of CYP4F2 c.1297A variant required a higher dose of acenocoumarol and warfarin than non-carriers (43.8 [35.0–60.2] vs. 35.0 [35.0–52.5] mg/week, p = 0.01; 35.0 [28.0–52.5] vs. 28.0 [28.0–42.0] mg/week, p = 0.05). Conclusions We have shown for the first time, that besides VKORC1 and CYP2C9 genetic variants, the CYP4F2 c.1297A and GGCX c.2084 + 45G have a moderate effect on VKAs dose requirements in Slavic population from Central-Eastern Europe." @default.
• W2034506206 created "2016-06-24" @default.
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• W2034506206 date "2014-09-01" @default.
• W2034506206 modified "2023-09-27" @default.
• W2034506206 title "Genetic determinants of acenocoumarol and warfarin maintenance dose requirements in Slavic population: A potential role of CYP4F2 and GGCX polymorphisms" @default.
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• W2034506206 doi "https://doi.org/10.1016/j.thromres.2014.06.022" @default.
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