福建省高血压人群7个高血压药物相关基因的多态性

Polymorphism analysis of seven hypertensive drug-related genes in hypertensive population in Fujian province

    摘要
  • 摘要: 目的 分析福建省高血压人群中7个高血压药物相关基因的多态性分布特征。方法 收集2020年11月至2022年9月在福建医科大学附属第一医院就诊的高血压患者540例，采用PCR-熔解曲线法检测7个高血压药物相关基因的多态性，统计其基因型频率和等位基因频率的分布情况，并进一步判断预期疗效和不良反应。结果 高血压患者540例β1-肾上腺素受体（ADRB1）1165G>C、细胞色素P450（CYP）2D6*10（CYP2D6*10）、CYP3A5*3基因的突变频率较高，分别为73.24%、56.85%、71.39%;心房钠尿肽前体A（NPPA）2238T>C、CYP2C9*3、血管紧张素Ⅱ1型受体（AGTR1） 1166A>C、血管紧张素转换酶（ACE）I/D基因的突变频率较低，分别为0.74%、3.15%、4.72%、32.78%。此外，分别有54.07%、15.56%、98.15%、100%、1.48%的患者对血管紧张素转换酶抑制药（ACEI）、血管紧张素受体阻滞药（ARB）、β受体阻滞剂、钙通道阻滞剂（CCB）、利尿剂的预期疗效在人群中属于较好及以上；分别有11.48%、57.23%、51.30%的患者对ACEI、β受体阻滞剂、CCB类药物发生不良反应的概率超过一般人群，但应用利尿剂、ARB类药物发生不良反应的风险较低。7个高血压药物相关基因的突变率在男性（354例）和女性（186例）高血压患者中差异无统计学意义；不同性别患者对同类高血压药物的预期疗效和预期不良反应差异亦无统计学意义（均P>0.05）。结论 福建省高血压患者选用β受体阻滞剂和CCB类药物疗效较好，但发生不良反应的概率也相应增加；选用利尿剂、ARB类药物疗效一般，但发生不良反应的风险较低。

     

    Abstract: Objective We aimed to analyze the distribution characteristics of seven hypertensive drug-related gene polymorphisms in the population with hypertension in Fujian province. Methods A total of 540 hypertensive patients were recruited at the First Affiliated Hospital of Fujian Medical University from November 2020 to September 2022. The PCR-melting curve method was used to detect the polymorphism of 7 hypertensive drug-related genes. The genotype and allele frequency distribution were analyzed, and the expected treatment responses and adverse effects were further evaluated. Results Among 540 hypertensive patients, the gene mutation frequency of β1 adrenergic receptor（ADRB1） 1165G＞C, cytochrome P450（CYP） 2D6*10（CYP2D6*10）, CYP3A5*3 was higher（73.24%, 56.85% and 71.39%, respectively） and the gene mutation frequency of natriuretic peptide precursor A（NPPA） 2238T＞C, CYP2C9*3, angiotensin Ⅱ type 1 receptor（AGTR1） 1166A＞C, angiotensin converting enzyme（ACE） I/D was lower（0.74%, 3.15%, 4.72% and 32.78%, respectively）. Besides, 54.07%, 15.56%, 98.15%, 100% and 1.48% patients exhibited a relatively stronger therapeutic response to angiotensin converting enzyme inhibitor（ACEI）, angiotensin Ⅱ receptor blocker（ARB）, β receptor blocker, calcium channel blocker（CCB） and diuretic, respectively. Moreover, the adverse effects of 11.48%, 57.23%, 51.30% patients to ACEI, β receptor blocker and CCB were higher than those of the general population. While patients treated with diuretic and ARB had a low risk of adverse effects. Compared with 354 male and 186 female hypertensive patients, there was no significant difference in the mutation rate of 7 hypertensive drug-related genes, and no significant difference in the expected treatment responses and adverse effects in different gender patients（P＞0.05）. Conclusions The data of hypertension drug-related gene polymorphism in hypertensive population in Fujian province showed that the therapeutic responses to β-blocker and CCB in hypertensive patients were higher, but the probability of adverse effects was also increased; and the therapeutic responses to diuretic and ARB were less effective, but the risk of adverse effect was low.

     

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