The impact of CYP4F2, ABCB1, and GGCX polymorphisms on bleeding episodes associated with acenocoumarol in Russian patients with atrial fibrillation.
Oral anticoagulants are commonly used to treat patients with thromboembolic pathology. Genetic variations could influence personal response to anticoagulant drugs. Acenocoumarol (AC) is a vitamin K antagonist used in anticoagulant therapy and as a prophylaxis measure in Europe. In this study, we assessed the effect of CYP4F2 rs2108622, ABCB1, and GGCX polymorphisms on the safety profile and regime dosing of AC in patients with nonvalvular atrial fibrillation.



Fifty patients aged 40-70 years were included. All patients received AC in the dose of 1-6 mg daily with a target international normalized ratio of 2.0-3.0. Genotyping for polymorphism markers C3435T for the ABCB1 gene, rs2108622 for the CYP4F2 gene, and rs11676382 for the GGCX gene were designed using polymerase chain reaction and restriction fragment length polymorphism. Statistical analysis was performed using the Fisher exact test and the Mann-Whitney U test.



We found that CYP4F2 rs2108622 CT carriers required a higher AC dose than CC (p=0.0366), and CT and TT carriers required a higher AC dose than CC (p=0.0314).



We found that ABCB1 CT and TT genotypes are associated with a higher risk of bleeding. No influence of ABCB1 and GGCX polymorphisms on the doses of AC was established. CYP4F2 could still be a genetic factor responsible for the personal variability of AC metabolism.
Dmitriy Alexeyevich
DA
Sychev
Aleksandr Vladimirovich
AV
Rozhkov
Ruslan Evgenyevich
RE
Kazakov
Anna Viktorovna
AV
Ananichuk
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000074:Acenocoumarol / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications* / Q000188:drug therapy / Q000235:genetics; D019735:Carbon-Carbon Ligases / Q000235:genetics*; D000072470:Cytochrome P450 Family 4 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012426:Russia
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000925:Anticoagulants; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase; D000074:Acenocoumarol