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

作　　者：商红艳[1,2] 姚小宝 荀振 杨滨[1,2] 欧启水[1,2] SHANG Hongyan;YAO Xiaobao;XUN Zhen;YANG Bin;OU Qishui(Department of Laboratory Medicine,Fujian Key Laboratory of Laboratory Medicine,Gene Diagnosis Research Center,Fujian Clinical Research Center for Laboratory Medicine of Immunology,The First Affiliated Hospital,Fujian Medical University,Fuzhou,Fujian 350005,China;Department of Laboratory Medicine,National Regional Medical Center,Binhai Campus of the First Affiliated Hospital,Fujian Medical University;The First Clinical College,Fujian Medical University)

机构地区：[1]福建医科大学附属第一医院检验科,福建省检验医学重点实验室,福建医科大学基因诊断研究中心,福建省临床免疫学检验临床医学研究中心,福建福州350005 [2]福建医科大学附属第一医院滨海院区国家区域医疗中心检验科 [3]福建医科大学第一临床医学院

出　　处：《中华高血压杂志》2023年第9期849-855,共7页Chinese Journal of Hypertension

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。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 β_1 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 th

关 键 词：高血压 抗高血压药基因 多态性 疗效 不良反应 

分 类 号：R544.1[医药卫生—心血管疾病]