Significance of CYP4F2 polymorphism on oral anticoagulation therapy with acenocoumarol in South Indian patients with mechanical heart valves

Abstract

BackgroundThe coumarin group of oral anticoagulants has a narrow therapeutic range and wide inter-individual variability. Polymorphism of VKORC1 and CYP2C9 genes are the major genetic determinants of the drug-dose response. Our study aimed to investigate the role of CYP4F2 (1347 G > A) polymorphism on the acenocoumarol daily dose requirement, and its interaction with VKORC1 and CYP2C9 polymorphism. Methods301 Rheumatic Heart Disease (RHD) patients with mechanical cardiac valves were recruited. Genotyping for CYP4F2, VKORC1 and CYP2C9 was done by PCR-RFLP. CYP4F2 genotype distribution GG, GA and AA was 23.5%, 51.5% and 25% respectively. The mean daily dose requirement for variant homozygous patients (AA) was 0.46 folds more when compared to wild type (GG) (Adjusted OR 0.46; 0.21–0.99, p = .048). However, on combined genotype analysis of CYP4F2, VKORC1 and CYP2C9 there was no significant difference in mean dose requirement. ConclusionThe homozygous genotype (AA) of CYP4F2 gene was more prevalent in our study cohort. No significant association was found between CYP4F2 gene polymorphism and acenocoumarol mean dose requirement, both when analyzed individually and in combination with VKORC1 and CYP2C9 polymorphisms.