ABCG2 Gene Polymorphisms Significantly Affect the Plasma Concentration of Rosuvastatin and Its Metabolites
OBJECTIVE To investigate the effect of pharmacokinetic-related gene polymorphisms of rosuvastatin on plasma con-centrations of rosuvastatin(RST)and its metabolites:rosuvastatin lactone(RSTL).METHODS The plasma concentrations of RST and its metabolites were determined through an established performance liquid chromatography mass spectrometry method And the plasma concentrations were determined and DNA was extracted in the Chinese group of 520 people who were stably taking RST for more than one week Nine SNPs in RST pharmacokinetics-related organic anion transporter,breast cancer resistance protein,cytochrome P450 enzyme genes were genotyped by using the Sequenom MassArray iPlex platform.Univariate and multiple linear regression were used to analyze the effects of baseline characteristics and gene polymorphisms on RST and RSTL respectively.RESULTS The reserch results revealed that ABCG2 rs2231142 variations were highly associated with the plasma concentrations of RST,RSTL(P＜0.05;RST:r2=9.7％;RSTL:r2=3.3％).SLCO1B1 rs4149056 significantly affected the concentrations of RST(P＜0.05,r2=1％).But,SLCO1B1 rs4149056 had no significant effect on the concentration of RSTL After inclusion in the multiple regression model,ABCG2 rs2231142,age,and creatinine were retained in the regression model(P＜0.05).CONCLUSION The effect of ABCG2 rs2231142 gene poly-morphisms on the plasma concentration of RST in the Chinese is greater than that of SLCO1B1 rs4149056.ABCG2 rs2231142 variations are the independent factor affecting the plasma concentrations of RST and RSTL.
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