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OBJECTIVE To investigate the effect of pharmacokinetic-related gene polymorphisms of rosuvastatin on plasma concentrations 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 polymorphisms 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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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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