β1受体A145G和G1165C多态性对比索洛尔治疗高血压疗效的影响

摘要

Objective To explore two common SNPs of β1 adrenergic receptor(Gly389Arg and Ser49Gly)on patients with essential hy-pertension(EH)and to study the association between these two SNPs of β1 - AR(Gly389Arg and Ser49Gly)and the efficacy of bisoprolol on es-sential hypertension,and to raise the level of clinical therapy to individuation and optimization by conducting the EH treatment to the gene level. Methods A total of 300 patients with mild or moderate essential hypertension were enrolled in the study group. Their WBC were used to extract DNA with PCR - RFLP. The polymorphism of β1 adrenergic receptor(Gly389Arg and Ser49Gly)had been analyzed. The individuals with their genotype of 49SS / 389AA,49SG/ 389AA,49SG/ 389GA and 49SS / 389GA were chosen to join the prospective clinical trial according to double blind rule. The dosage regimen of bisoprolol was 2. 5 mg qd,and the course of treatment was 4 weeks. Their HR and BP were measured every week. The data of measurement were compared. Results As to condon 389 and 49,the resting HR,SBP,DBP and MBP of patients with 4 geno-types were different after administration of bisoprolol for 4 weeks( P < 0. 05). The resting HR,SBP,DBP and MBP of patients with 49SG/389AA were higher than those of other groups( P < 0. 05). The above indexs of patients with 49SS/ 389GA were lower than those of other groups ( P < 0. 05). Conclusion Patients with 49SS/ 389GA genotype were associated with better response to bisoprolol and they may gain more bene-fits from bisoprolol for treatment of essential hypertension.%目的：探讨比索洛尔对高血压患者的疗效及β1肾上腺素受体 A145G 与 G1165C 多态性的关系，以期能从基因水平指导高血压病的治疗。方法收集300例轻中度高血压患者（研究组），另选同期体检健康人群300例（对照组），采用 PCR - RFLP 方法从白细胞中提取 DNA，进行β1肾上腺素受体 A145G 突变（Ser49Gly）及 G1165C 突变（Gly389Arg）基因分型。从所有患者中选择49SS/389AA、49SG/389AA、49SG/389GA 与49SS/389GA 个体采用双盲法进行前瞻性临床实验。临床给药方案为比索洛尔2.5 mg/ d 一次口服，治疗疗程为4周。比较两组间及组内心率及血压水平。结果对于位点389和位点49，4种基因型患者静息心率、舒张压、收缩压、平均动脉压差异有显著性（ P <0.05），基因型为49SG/389AA 的患者静息心率、舒张压、收缩压、平均动脉压较其它三组明显增加，差异有显著性（ P <0.05）。49SS/389GA 基因型患者经比索洛尔治疗后静息心率、舒张压、收缩压、平均动脉压降低幅度比49SS/389AA、49SG/389AA、49SG/389GA 基因型患者显著，差异具有统计学意义（ P <0.05）。结论高血压患者中基因型为49SS/389GA的患者应用索洛尔产生的心血管效应和治疗效果更为显著。