OCT1基因rs2282143 rs628031和rs36056065多态性对二甲双胍药代动力学的影响

目的 探讨有机阳离子转运体1（OCT1）基因中 rs2282143（P341L ，1022C＞ T）、rs628031（M408V ，1222A＞G）和rs36056065（ins/del GTAAGTTG）多态性对二甲双胍药代动力学的影响。方法 65例男性健康自愿者空腹口服盐酸二甲双胍片500 mg ，采用液相色谱-串联质谱法测定血浆中二甲双胍的浓度，并根据rs2282143、rs628031和rs36056065多态性进行分组。结果 rs2282143多态性中CC、C T 和 T T分别为45例（69．2％）、19例（29．2％）和1例（1．5％），CC 和 CT 组间的 Cmax 、Tmax 、AUC0-t 、AUC0-∞和 T1/2差异无统计学意义（P＞0．05）。rs628031与rs36056065等位基因完全连锁，其中 AA/ins、AG/ins-del 和 GG/del 分别为8例（12．3％）、24例（36．9％）和33例（50．8％）。AG/ins-del的Cmax 、AUC0-t 、AUC0-∞显著高于 AA/ins和GG/del ，差异有统计学意义（P＜0．05），AA/ins和GG/del之间差异无统计学意义（P＞0．05）；Tmax 、T1/2在3种基因型间差异无统计学意义（P＞0．05）。结论 rs2282143多态性与二甲双胍药代动力学无相关性，完全连锁的 rs628031和 rs36056065与二甲双胍药代动力学密切相关。

Effects of OCT1 gene rs2282143,rs628031 and rs36056065 polymorphism on metformin pharmacokinetics in healthy subjects

Objective To explore the effects of organic cation transporter 1（OCT1） gene rs2282143（P341L , 1022C〉 T） ,rs628031（M408V ,1222A〉 G） and rs36056065（ins/del GTAAGTTG） polymorphisms on metformin pharmacokinetics in healthy volunteers .Methods 65 healthy men were given a single oral dose of 500 mg metformin , and the plasma concentrations of metformin were measured for up to 24 h by LC-MS/MS .The subjects were divided into different groups according to polymorphisms of rs2282143 ,rs628031 and rs36056065 .Results The allele CC ,CT and TT of the rs2282143 were 45（69 .2% ） ,19（29 .2% ） and 1（1 .5% ） in 65 subjects ,respectively .There was no difference of Cmax ,Tmax ,AUC0-t ,AUC0-∞ and T1/2 between CC and CT in the rs2282143 .The polymorphisms rs628031 and rs36056065 were completely linkage disequilibrium and the presence of allele AA/ins、AG/ins-del and GG/del were 8（12 .3% ） ,24（36 .9% ） and 33（50 .8% ） in our subjects ,respectively .The Cmax ,AUC0-t ,AUC0-∞ of allele AG/ins-del were significantly higher than the allele AA/ins and GG/del ,whereas no difference was observed between the allele AA/ins and GG/del ,respectively （P〈 0 .05） .For the comparison of Tmax and T1/2 ,there were no difference among the allele AA/ins ,AG/ins-del and GG/del（P〉0 .05） .Conclusion There was no effect of the polymorphism rs2282143 on metformin pharmacokinetics .The polymorphisms rs628031 and rs36056065 that were in completely linkage disequilibrium significantly associated with metformin pharmacokinetics .