MDR1基因C3435T多态性对替米沙坦稳态血药浓度及降压疗效的影响

Effects of MDR1 gene C3435T polymorphism on the steady-state plasma concentration and hypotensive activity of telmisartan

目的:探讨多药耐药基因MDR1 C3435T(exon 26)位点基因多态性对替米沙坦在原发性高血压患者中的稳态血药浓度及降压疗效的影响。方法:采用聚合酶链反应(PCR)和限制性内切酶片段多态性(RFLP)的方法对连续30 d每天口服40 mg替米沙坦的61名高血压患者的MDR1C3435T位点进行基因分型。使用高效液相色谱-荧光检测法(HPLC-FLD)测定高血压患者的稳态血药浓度,使用水银血压计测量治疗前、后高血压患者的血压值。比较不同基因型间高血压患者的稳态血药浓度及降压疗效的差异。结果:在61例中老年原发性高血压患者中,MDR1 C3435T CC型纯合子的频率为39.34%,TT型纯合子的频率为11.48%,CT型杂合子的频率为49.18%,MDR1C3435T位点等位基因发生率在健康人群和高血压患者间差异无统计学意义。3种基因型高血压患者的稳态血药浓度及降压有效率间差异无统计学意义(P>0.05)。结论:MDR1 C3435T位点的基因多态性与高血压患者的稳态血药浓度及降压疗效间无相关性。

AIM： To study the effects of MDR1 C3435T polymorphism on steady-state plasma concentration and hypotensive activity of telmisartan. METHODS： 61 cases of essential hypertension patients were received oral dose of 40 rng telmisartan per day for 30 days. The genotyping of the MDR1 C3435T polymorhism in the patients was performed by using method of pelymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. The plasma concentrations of telmisartan were determined by high performance liquid chromatograpy-Fluorescence detector （HPLC-FLD）. The blood pressures of the patients were measured before and after treatment. The plasma concentrations and therapeutic effect of telmisartan were compared among the three different genotype groups. RESULTS： Among the 61 cases of elderly hypertension patients, the frequencies of 3435CC, 3435TT and 3435CT were 39.34%, 11.48% and 49.18%, respectively. There were no differences between healthy people and the hypertension patients in allele frequencies of MDR1 C3435T. The telmisartan steady-state concentration and curative effect also had no significant differences among the three genotype groups in the hypertensive patients. CONCLUSION： The MDR1 C3435T polymorphism does not affect the steady-state plasma concentrate and curative effect of telmisartan in hypertension patients.