社区H型高血压患者药物基因作用靶点多态性分布及叶酸联合维生素D干预效果研究  

Distribution of Pharmacogenetic Polymorphisms and the Intervention Effects of Folic Acid Combined with Vitamin D in Community-based Patients with H-type Hypertension

作　　者：庞爱梅[1] 高伟 张恒[1] 蒲双双[1] 郭莉莉 范子荣 刘海霞 刘瑞霞[1] PANG Aimei;GAO Wei;ZHANG Heng;PU Shuangshuang;GUO Lili;FAN Zirong;LIU Haixia;LIU Ruixia(Department of Laboratory/Geriatrics Medicine and Health Care,Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250011,China;Jinan Hehe Medical Laboratory,Jinan 250021,China)

机构地区：[1]山东中医药大学附属医院检验科,山东中医药大学附属医院老年医学保健科,山东省济南市250011 [2]济南和合医学检验所,山东省济南市250021

出　　处：《中国全科医学》2024年第6期704-710,共7页Chinese General Practice

基　　金：中华国际科学交流基金会检验检测科技专项基金(Z2020LSD019)。

摘　　要：背景H型高血压严重影响着人们的健康及生活质量,目前临床上治疗高血压主要根据患者症状和临床经验选择药物,降压效果不理想,急需探寻降压药物基因分布的多态性,为高血压患者进行个体化用药指导。目的探讨济南市社区H型高血压药物作用靶点基因多态性分布及叶酸联合维生素D的干预作用,为该地区开展高血压医防融合精准医疗提供参考依据。方法2020年6月—2022年6月随机抽取山东省济南市槐荫区20家街道办事处社区卫生服务中心200例血压控制不佳的高血压患者为研究对象,治疗前首先进行5类常用抗高血压药物[利尿剂、β受体阻滞剂、血管紧张素转化酶抑制剂(ACEI)、钙离子通道抑制剂(CCB)、血管紧张素Ⅱ受体拮抗剂(ARB)]相关高血压个体化用药基因位点的基因多态性检测。将患者随机分为基因导向治疗组(基因组)与基因导向协同叶酸、维生素D治疗组(基因导向组),每组100例。基因组根据检测的高血压基因作用位点的特点调整用药;基因导向组在基因组治疗方案的基础上同时服用叶酸、维生素D。干预初始(M0)、干预3个月(M3)、干预6个月(M6)时采集患者晨间未服用降压药物情况下坐位收缩压和舒张压。记录患者患病情况、不良反应发生情况、脑卒中发生情况,进行基因测序,检测血清同型半胱氨酸(Hcy)浓度。采用Pearson相关性分析或Spearman秩相关分析探究性别、年龄、收缩压、舒张压与Hcy的相关性。结果研究对象性别(r_(s)=-0.463)、收缩压(r=0.181)、舒张压(r=0.188)与Hcy水平有相关性(P<0.05)。5类抗高血压药物基因作用靶点中,与药物代谢酶基因多态性位点相关的分别是CYP3A5(A6986G)、CYP2C9(c.1075A>C)、CYP2D6(c.100C>T),与药物作用靶点敏感性基因多态性位点相关的是ADRB1、ACEI(I/D)、AGTR1、NPPA。基因组A6986G:CYP3A5*1/*1(AA)、ACEI(I/D):D/D、c.100 C>T:CYP2D6*1/*1(CC)患者M3、M6舒张压Background H-type hypertension seriously affects people's health and quality of life.Currently,the clinical treatment of hypertension mainly selects drugs based on the experience,and the antihypertensive effect is not ideal.It is urgent to explore the pharmacogenetic polymorphisms of antihypertensive drugs and provide individualized medication guidance for hypertensive patients.Objective To investigate pharmacogenetic polymorphisms and the intervention effects of folic acid combined with vitamin D in patients with H-type hypertension in Jinan community,and provide reference for the implementation of integrated precision medicine for hypertension.Methods From June 2020 to June 2022,200 hypertensive patients with poorly controlled blood pressure in 20 community health service centers of Huaiyin District,Jinan City,Shandong Province were randomly selected as the research objects.Before treatment,the gene polymorphisms of five commonly used individualized antihypertensive drugs,including diuretics,β-blockers,angiotensin-converting enzyme inhibitors(ACEI),calcium channel inhibitors(CCB),angiotensin-Ⅱreceptor antagonists(ARB),were detected.Patients were randomly divided into the gene-directed treatment group(genome group)and gene-directed synergistic folic acid and vitamin D treatment group(gene-directed group),with 100 cases in each group.The genome group adjusted the drug according to the characteristics of the detected hypertension gene loci;the gene-directed group received folic acid and vitamin D in addition to the genomic therapy regimen.Sitting systolic and diastolic blood pressures in the morning without antihypertensive drugs were collected from patients at the initial intervention(M0),3 months of intervention(M3),and 6 months of intervention(M6).Case status,adverse reactions and stroke were recorded,gene sequencing was performed,and serum homocysteine(Hcy)concentration was detected.Pearson correlation analysis or Spearman's rank correlation analysis were used to explore the correlation between sex,age,syst

关 键 词：高血压 高同型半胱氨酸血症 H型高血压 基因多态性 叶酸 维生素D 

分 类 号：R544.1[医药卫生—心血管疾病]