The Influence Of PXR And OATP1B1 Gene Polymorphism On Therapeutic Dose Of Warfarin

Aims: Warfarin dose requirement was influenced by many gene polymorphisms. Nuclear receptor PXR is a transcriptional control factor and control the expression of genes related to metabolism and transport process of warfarin.OATP1B1 can transport the endogenic and exogenous ligands of PXR. Forthcoming researches indicated that these two gene polymorphisms are likely to influence warfarin dose requirement. The aim of this present study is to view if there is contribution of PXR and OATP1B1 gene polymorphism to warfarin dose requirement.Methods: Basic clinical feature and blood samples were collected from 139 Chinese patients received mechanicalness cardiac valve replacement with stable warfarin dose requirement and an international normalized ratio (INR) of the prothrombin time within the target range of 1.5-3.0.OATP1B1-T521C genotype were determined using PCR-RFLP method.NR1I2-G7635A and A11156C genotype were determined by pyrosequencing sequenator. Warfarin dose were compared between the genotypes of these three polymorphisms and relationship between warfarin dose requirement and these polymorphisms were analyzed. The contribution of gender, age and body weight to warfarin dose requirement were also investigated.Results: The daily mean warfarin dose requirement of patients who has at least one 521 C mutant allele is significant lower than the patients without C mutant allele (2.59±0.66mg vs 3.04±1.03mg, P=0.039).When compared between the respective three genotypes of NR1I2-G7635A and A11156C, there is no difference in patients' warfarin dose requirement (p=0.769,p=0.805). The distinction between the daily mean dose of male and female patients has no statistical significance(3.12±1.07mg vs 2.86±0.93mg, P=0.133).And there is also no correlation between patients' dose requirement and age (P=0.795). but the linear correlations between warfarin dose requirement and body weight is significant (P=0.048).Conclusions: Our study found that neither NR1I2-G7635A polymorphism nor A11156C polymorphism has significant influence on patients' warfarin dose requirement. However, OATP1B1-T521C polymorphism has contribution to warfarin dose. Age and gender has no influence on patients' warfarin dose requirement,but body weight can positively influence patients' warfarin dose requirement.