Investigation Of The Relationship Between The Variation Of Inter-individual Warfarin Dosing And The Pharmacogenomics

Objective The purpose of this study is to establish warfarin dosing model based on the genetic and the non-genetic factors to guide the warfarin replacement,thromboembolism and the atrial fibrillation that achieved the steady state of anticoagulant. The PCR-hybridization was used for genotyping of Cytochrome P450 2C9 *1/*3(CYP2C9 *1/*3) and Vitamin K epoxide reductase complex subunit 1-1639-A/G(VKORC1-1639-A/G) in patients with oral warfarin anticoagulation. We collected patient’s non-genetic information including age, gender, height, weight and stable warfarin dose. The T‐Test was using in the preliminary comparison of warfarin dose in gender and different genotype. Using Pearson correlation coefficient to analyze the warfarin dose relation with age and BMI. Multiple linear regression was applied to the analysis of warfarin dose and the relationship among these aboved variables to deduce a new dosage regimen. Results Via the preliminary analysis, the mean dosage of warfarin of male was 3.00±1.06 mg/day, while the women was 2.80±0.96mg/day mg/day, there is no significant difference between male and female patients in warfarin dosage(P > 0.05). Warfarin dose is negatively related to the age(r=-0.276,P=0.030), and positive correlation with BMI(r=0.142, P=0.030). There is no significant difference in the genotype VORC1 AA and AG in warfarin dosage, so as the CYP2C9 * 1 * 3 and * 1 * 1(P > 0.05). The established multiple linear regression model including age, body mass index(BMI), CYP2C9 *1/*3 and VKORC1-1639-A/G genotype could explain the inter-individual variation in warfarin dose requirement of 21.2%. The warfarin dose predicting formula is deduced by the analysis of the multiple linear regression: Y=2.752-0.021×age+0.067×BMI+1.104×CPY2C9-1.017×VKORC1. The established formula will help clinicians to predict patients dosage of warfarin precisely. Conclusion The warfarin dosing formula based on clinical and pharmacogenomics will help to effectively improve the safety of warfarin anticoagulation.