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Objective: To investigate the effect of genetic polymorphisms in VKORC1, CYP2C9, GGCX, EPHX1, APOE genes on inter-individual variation in warfarin maintenance dose., Methods: Two hundred and forty-nine patients with stable warfarin dose were enrolled in this study, and the clinical data and blood samples of the patients were collected. Genotypes for the 5 genes were determined by using PCR and denaturing high performance liquid chromatography (DHPLC) assay. The warfarin maintenance doses were compared among patients with different genotypes of the 5 genes, and a warfarin stable dosing algorithm was derived based on genetic and non-genetic factors., Results: Of the 5 genes, VKORC1, CYP2C9 and GGCX were associated with warfarin stable dose. The multiple linear regression analysis indicated that VKORC1, CYP2C9 and GGCX genes, age and weight, had significant influence on inter-individual variation in warfarin stable dose, which contributed 30.2%, 22.8%, 1.5%, 4.7% and 6.7% respectively. The warfarin stable dosing algorithm acquired from the optimal regression model could explain 57.8% variation in warfarin dose., Conclusion: This study suggested that genetic factors are the major determinants of the warfarin maintenance dose, and warfarin stable dosing algorithm may be useful for helping clinicians to prescribe warfarin with greater safety and efficiency.

Objective: To investigate the effects of AICAR on the activity of transcription factor FOXO1 and expression of ubiquitin ligase MuRF1 in rat cardiomyocytes, and explore the possible role of AMP-activated protein kinase (AMPK) in proteolysis pathways., Methods: In vitro cultured neonatal rat cardiac myocytes were treated with AICAR, and Western blotting was used to detect the phosphorylation of FOXO1 and expression of MuRF1 in the cells., Results: AICAR activated AMPK in rat cardiac myocytes. Activated AMPK significantly inhibited the phosphorylation of FOXO1 and increased MuRF1 protein expression., Conclusion: AMPK may regulate proteolysis by activating FOXO1 transcription factor and up-regulating MuRF1 expression.