高迁移率族蛋白1基因多态性与中国南方农村常用高血压药物疗效的关系

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (7): 766-771.

高迁移率族蛋白1基因多态性与中国南方农村常用高血压药物疗效的关系

郭道遐¹, 陈燕春², 王林红¹, 鲁玮¹, 沈冲³, 杨松², 赵祥海², 金岳龙¹, 姚应水¹

¹ 皖南医学院公共卫生学院流行病与卫生统计学教研室,芜湖 241002,安徽;
² 江苏大学附属宜兴市人民医院心内科,宜兴 214200,江苏;
³ 南京医科大学公共卫生学院流行病与卫生统计学系,南京 210029,江苏

收稿日期:2013-11-12 修回日期:2014-06-30 发布日期:2014-07-21
通讯作者: 姚应水,男,教授, 硕士生导师,研究方向:慢性病分子流行病学。 Tel: 0553?3932059 　E?mail: yingshuiyao@163.com
作者简介:郭道遐,女,在读硕士研究生,研究方向:慢性病流行病学。 Tel: 15295533601 E-mail: daoxiakuo@163.com。陈燕春,并列第一作者,男,硕士,研究方向:心血管疾病治疗。 Tel: 13815115738 E-mail: chenyanchun@mednial.com.cn
基金资助:
国家自然科学基金项目(81072367,81273165); 安徽省自然科学基金项目(1308085MH135)

Association of HMGB1 gene polymorphism and drug treatment in patient with essential hypertension

GUO Dao-xia¹, CHEN Yan-chun², WANG Lin-hong¹, LU Wei¹, SHEN Chong³, YANG Song², ZHAO Xiang-hai², JIN Yue-long¹, YAO Ying-shui¹

¹ Department of Epidemiology and Biostatistics, School of Public Health, Wannan Medical College, Wuhu 241002, Anhui,China;
² Department of Cardiology,Affiliated Yixing People' s Hospital of Jiangsu University,Yixing 214200,Jiangsu,China;
³ Department of Epidemiology and Biostatistics,School of Public Health,Nanjing Medical University,Nanjing 210029, Jiangsu,China

Received:2013-11-12 Revised:2014-06-30 Published:2014-07-21
About author:WANG Ping,female,postgraduate student,engaged in the study of clinical pharmacy and personalized medicine. Tel: 0371⁃84327265 　E⁃mail:wangliu200798@126.com

摘要/Abstract

摘要： 目的研究参与AGER氧化损伤通路的高迁移率族蛋白1(HMGB1)基因的遗传变异对于高血压药物效果的影响。方法采用流行病学现况调查方法,对服用复方利血平、珍菊降压片和降压片的高血压患者(780例)进行流行病学和临床生化指标资料的收集。位点选择采用连锁不平衡分析和生物信息学的功能预测相结合的方法,选择HMGB1基因的3个标签单核苷酸多态性(tagSNPs)与服用不同降压药物后人群血压水平的关系。结果服用复方利血平的高血压病人中,rs1412125位点与舒张压水平呈线性负相关,携带CC等位基因的病人舒张压水平明显低于TT和TC等位基因,调整混杂因素后P值为 0.040。服用珍菊降压片的女性高血压病人中,rs1045411的G到A的突变和rs2249825的C到G的突变,收缩压都有明显的下降,校正混杂因素后P值分别为 0.044、0.043。服用降压片的≥55岁人群中,rs2249825位点不同基因型之间的收缩压的差异,校正协变量后仍有统计学意义(P=0.048)。结论 HMGB1基因多态性可能影响复方利血平、珍菊降压片和降压片的降压效果。

关键词: HMGB1基因, 基因多态性, 原发性高血压, 高血压药物, 治疗效果

Abstract: AIM: To explore the effect of HMGB1 gene polymorphism on drug treatment in patient with essential hypertension, to raise cure rate of hypertension patients by reasonable cure. METHODS: A cross-sectional study of 780 patients with hypertension that were recruited by taking compound reserpine, Zhen Ju Jiang Ya Tablet and Jiang Ya Tablet, was conducted and three tagging single nucleotide polymorphisms (tagSNPs) of HMGB1 gene (rs1045411, rs1412125, rs2249825) were selected by linkage disequilibrium (LD) analysis and functional prediction. A quantitative trait analysis was performed for evaluating the relation between HMGB1 genetic variation and blood pressure by taking different antihypertensives drugs.RESULTS:In hypertensive taking compound reserpine, after adjusting the confounding factors, diastolic blood pressure (DBP) linearly decreased with the variation (T>C) of rs1412125 (P=0.040). In female hypertensive taking Zhen Ju Jiang Ya Tablet,after adjusting the covariant, systolic blood pressure(SBP) significantly decreased with the variation(G>A) of rs1045411 and the variation (C>G) of rs2249825 respectively (P=0.044 and 0.043). In age≥55 hypertensive taking Jiang Ya Tablet, different genotypes were significantly different after adjusting the covariant(P=0.048). CONCLUSION: HMGB1 gene might affect the antihypertensive effect of compound reserpine, Zhen Ju Jiang Ya Tablet and Jiang Ya Tablet.

Key words: HMGB1 gene, gene polymorphism, essential hypertension, hypotensive drugs, therapeutic effect

中图分类号:

郭道遐, 陈燕春, 王林红, 鲁玮, 沈冲, 杨松, 赵祥海, 金岳龙, 姚应水. 高迁移率族蛋白1基因多态性与中国南方农村常用高血压药物疗效的关系[J]. 中国临床药理学与治疗学, 2014, 19(7): 766-771.

GUO Dao-xia, CHEN Yan-chun, WANG Lin-hong, LU Wei, SHEN Chong, YANG Song, ZHAO Xiang-hai, JIN Yue-long, YAO Ying-shui. Association of HMGB1 gene polymorphism and drug treatment in patient with essential hypertension[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(7): 766-771.

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