抗高血压药物基因检测在慢性肾衰竭难治性高血压患者中的应用

Application of genetic testing in individualized antihypertensive medication for chronic renal failure patients complicated with resistant hypertension

目的:探讨慢性肾衰竭难治性高血压患者高血压基因多态性分布以及靶向降压对血压控制及心脑血管事件的影响。方法:慢性肾衰竭难治性高血压患者随机入组经验降压组和靶向降压组,经验降压组予以经验性调整降压药物,靶向降压组基于高血压个体化用药基因CYP2D6*10、CYP2C9*3、ADRB1(1165G>C)、AGTR1(1166A>C)、ACE(I/D)、NPPA(2238T>C)、CYP3A5*3检测结果靶向选择降压药物,观察基因多态性分布,比较两组患者血压达标率、心脑血管事件发生率。结果:突变频率较高的有CYP3A5*3(79.17%)、CYP2D6*10(76.67%);突变频率较低的有NPPA(0.00%)、ACE(I/D)(9.17%);CYP2C9*3突变频率为28.33%。靶向降压组治疗第7天血压治疗达标率(85.00%)高于经验降压组(48.00%)(P<0.001);且靶向降压组随访3个月内心脑血管事件发生率(10.00%)低于经验降压组(32.00%)(P<0.05)。结论:慢性肾衰竭难治性高血压患者基因多态性具有明显的群体差异,基于抗高血压药物基因检测结果合理调整用药,对高血压患者降压具有指导意义。

Objective:To investigate the distribution of hypertension gene polymorphisms and the effect of targeted antihypertensive therapy on blood pressure control and cardio-cerebrovascular events in chronic renal failure patients complicated with resistant hypertension.Methods:Chronic renal failure patients complicated with resistant hypertension were randomly divided into empirical antihypertensive treatment group(group A)and targeted antihypertensive therapy group(group B).Patients in group A and group B received empirical antihypertension medication and targeted medication based on genetic testing of CYP2D6*10,CYP2C9*3,ADRB1(1165G>C),AGTR1(1166A>C),ACE(I/D),NPPA(2238T>C)and CYP3A5*3 respectively.Distribution of gene polymorphisms was evaluated.The blood pressure control rate and the incidence of cardio-cerebrovascular events were compared between two groups.Results:CYP3A5*3(79.17%)and CYP2D6*10(76.67%)were the most common mutations.NPPA and ACE(I/D)mutation were less frequent(0.00%and 9.17%respectively).CYP2C9*3 mutation frequency was 28.33%.Group B had significantly higher blood pressure control rate on the 7 th day of treatment than group A(85.00%vs.48.00%,P<0.001)and significantly lower incidence of cardio-cerebrovascular events within 3-month follow-up(10.00%vs.32.00%,P<0.05).Conclusion:There are significant gene polymorphisms differences among chronic renal failure patients complicated with resistant hypertension.Reasonable medication adjustment based on genetic testing is of great significance for controlling blood pressure.