Effects of VKORC1 and CYP2C9 gene polymorphisms on the stable dosage of warfarin and anticoagulation in patients with hypertrophic cardiomyopathy complicated with atrial fibrillation

Abstract

Objective To investigate the gene polymorphisms and clinical features of vitamin K epoxide reductase complex 1(VKORC1) and cytochrome P450 2C9(CYP2C9), and their correlation with stable dosage of warfarin, the risk of hemorrhage and over anticoagulation for patients with hypertrophic cardiomyopathy. Methods A retrospective study was performed on 60 patients with hypertrophic cardiomyopathy(HCM) combined with atrial fibrillation(AF) who were admitted and regularly took oral warfarin as anticoagulation from January 2011 to December 2016.The clinical data such as age, body height, body weight, stable warfarin dosage and the situation of hemorrhage and over anticoagulation were recorded.Genotypes of CYP2C9 and VKORC1 were detected with fluorescence PCR-capillary electrophoresis sequencing and the relationship between the genotype and clinical features and the stable dose of warfarin, hemorrhage and over anticoagulation were analyzed by statistical methods. Results Among the 60 patients, VKORC1-1639G>A detection showed that 50 patients were AA type, 9 patients were AG type, 1 patient was GG type, the stabledosage of AA type patients were significant lower than that of AG type patients(P 0.05); CYP2C9 detection showed that 51 patients were *1/*1 type, 6 patients were *1/*3 type, 3 patients were *3/*3 type, *2 allele was not found, the stable dosage of patients who carry the *3 mutation were significant lower than that of *1/*1 type patients, and the more *3 mutation they own, the lower dosage they require(P 0.05). The incidence of hemorrhage and anticoagulation was significantly higher in patients aged 65 years or older than those who were younger than 65 years(P<0.05). Conclusion Stable warfarin dosage has relationship with different genotypes of VKORC1 and CYP2C9 in HCM patients, age may be a factor of warfarin over anticoagulation and hemorrhage. Key words: Hypertrophic cardiomyopathy; Atrial fibrillation; Warfarin; Vitamin K epoxide reductase complex 1; cytochrome P450 2C9; Gene polymorphisms; Hemorrhage; Over anticoagulation