Xiao Zhi-Lin, Yang Mei, Chen Xiao-Bin, Xie Xiu-Mei, Chen Mei-Fang
Department of Geriatric Cardiology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Department of Cardiology, Xiangya Hospital, Central South University, Changsha, China.
Cardiovasc Diagn Ther. 2022 Oct;12(5):635-645. doi: 10.21037/cdt-22-154.
The implementation of genotyping for anti-hypertensive drugs in clinical practice remains a challenge. We conducted this study to analyze the distribution of polymorphisms of antihypertensive drug-related genes in Changsha County in China and compare the clinical effectiveness of genotype-guided and clinical experience-guided antihypertensive therapy in hypertensive individuals.
A total of 9,933 essential hypertensive participants from Changsha County were consecutively enrolled in our study, and 7 genetic polymorphic loci (, , , , , and ) were detected by a polymerase chain reaction (PCR)-fluorescence probe. From an available sample of 660 hypertensive participants, 495 cases were randomly identified by genotype-guided therapy and 165 cases by clinical experience-guided therapy. We performed 24-hour ambulatory blood pressure (BP) monitoring on each of these cases, pre- and post-intervention.
In the enrolled 9,933 cases, the mutation frequencies of , , , *, , and were 4.41%, 74.60%, 5.55%, 57.08%, 30.94%, 69.03% and 1.19%, respectively. In both genotype-guided and clinical experience-guided groups, the comparisons of intra-group pre-and post-treatments showed significant decreases in diastolic blood pressure (DBP) (P<0.01) and significant increases in the control rate of BP (47.1% 38.6% and 37.5% 33.9%, P<0.05) in response to adjusted antihypertensive agents. Correspondingly, the extent of the reduction of systolic blood pressure (SBP; 3.52±11.72 0.92±9.14 mmHg), the extent of the increase in the rate of BP control (8.5% 3.6%) and the percentage rate of decrease of grades 2 and 3 hypertensive individuals were more significant in the genotype-guided group than that in the clinical experience-guided group (P<0.01).
While prescribing anti-hypertensive drugs, appropriate dosage and type adjustments should be made according to the gene mutation frequency and individual circumstances. Pharmacogenomics-guided personalized treatment of hypertensive patients is likely to be a more effective strategy, especially in those with significantly elevated SBP.
在临床实践中实施抗高血压药物基因分型仍面临挑战。我们开展本研究以分析中国长沙县抗高血压药物相关基因多态性的分布情况，并比较基因分型指导和临床经验指导的抗高血压治疗在高血压患者中的临床疗效。
连续纳入来自长沙县的9933例原发性高血压参与者，通过聚合酶链反应（PCR）-荧光探针检测7个基因多态性位点（、、、、、和）。从660例高血压参与者的可用样本中，随机确定495例接受基因分型指导治疗，165例接受临床经验指导治疗。对这些病例在干预前后均进行24小时动态血压监测。
在纳入的9933例病例中，、、、*、、和的突变频率分别为4.41%、74.60%、5.55%、57.08%、30.94%、69.03%和1.19%。在基因分型指导组和临床经验指导组中，组内治疗前后比较显示，使用调整后的抗高血压药物后舒张压（DBP）显著降低（P<0.01），血压控制率显著提高（47.1%对38.6%，37.5%对33.9%，P<0.05）。相应地，基因分型指导组收缩压（SBP）降低幅度（3.52±11.72对0.92±9.14 mmHg）、血压控制率提高幅度（8.5%对3.6%）以及2级和3级高血压患者的降低百分比均比临床经验指导组更显著（P<0.01）。
在开具抗高血压药物时，应根据基因突变频率和个体情况进行适当的剂量和类型调整。药物基因组学指导的高血压患者个体化治疗可能是一种更有效的策略，尤其是在SBP显著升高的患者中。
