胰岛素样生长因子1基因多态性与常用抗高血压药物治疗后血压水平的关联研究

doi:10.12092/j.issn.1009-2501.2019.02.009

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (2): 171-179.doi: 10.12092/j.issn.1009-2501.2019.02.009

胰岛素样生长因子1基因多态性与常用抗高血压药物治疗后血压水平的关联研究

陈燕¹，朱丽君¹，方正美¹，朱汇¹，金岳龙¹，沈冲²，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:2018-10-24 修回日期:2018-12-27 出版日期:2019-02-26 发布日期:2019-03-04
通讯作者: 姚应水，男，教授，研究方向：流行病与卫生统计学。 E-mail:yingshuiyao@163.com
作者简介:陈燕，女，硕士，实验师，研究方向：慢性病流行病学与医学统计学。 E-mail：bingyan-1209@163.com 朱丽君，并列第一作者，女，硕士，助教，研究方向：慢性病流行病学与医学统计学。 E-mail：381491908@qq.com
基金资助:
国家自然科学基金（81673266，81541071）；安徽省重点研究和开发计划项目（1804h08020261）；安徽省自然科学基金项目（1808085QH283，1808085MH297）

Association of insulin-like growth factor(IGF)-1 polymorphisms and efficacy of antihypertensive drugs

CHEN Yan¹, ZHU Lijun¹, FANG Zhengmei ¹,ZHU Hui ¹, JIN Yuelong¹, SHEN Chong², YAO Yingshui¹

¹Department of Epidemiology and Biostatistics, School of Public Health, Wannan Medical College, Wuhu 241002, Anhui, China; ² Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, China

Received:2018-10-24 Revised:2018-12-27 Online:2019-02-26 Published:2019-03-04

摘要/Abstract

摘要：

目的: 探讨胰岛素样生长因子1（IGF-1）基因多态性与抗高血压药物治疗后血压水平的关联性。方法: 运用流行病学现况调查方法，收集服用复方利血平、降压片和珍菊降压片的780例高血压患者的一般临床特征并测量其血压和临床生化指标。选择IGF-1基因的5个标签位点，采用TaqMan技术进行基因分型。采用协方差分析及分层分析对其基因多态性与药物治疗后血压水平的关系进行评价。结果: 在服用降压片的高血压病人中，rs6219位点不同基因型之间舒张压水平差异有统计学意义（P=0.01）。在服用复方利血平的高血压病人中，rs5742612和rs6218位点不同基因型之间收缩压水平差异有统计学意义（P值分别为0.04、0.017）。在服用珍菊降压片的高血压患者中，rs6218位点不同基因型之间舒张压水平及rs6219位点不同基因型之间收缩压水平差异均有关联（P值分别为0.017、0.033）。进一步分层分析发现，服用降压片的患者中，随着rs35767位点遗传变异女性收缩压的水平呈线性下降，而男性舒张压水平呈线性上升，校正混杂因素后P值分别为0.028、0.038。结论: IGF-1基因多态性与复方利血平、降压片和珍菊降压片三种抗高血压药物治疗后血压水平均有显著相关，提示IGF-1基因可能是高血压重要的药物疗效生物标记。

关键词: 胰岛素样生长因子1, 基因多态性, 抗高血压药物, 血压水平

Abstract:

AIM: To evaluate the association between IGF-1 genetic polymorphisms and blood pressure response to antihypertensive drugs. METHODS:A case-sectional study of 780 hypertension patients taking compound reserpine, Jiang Ya Tablet and Zhenju Jiang Ya Tablet were recruited.Five tagging single nucleotide polymorphisms of IGF-1 gene (rs5742612, rs35767, rs6214, rs6218, rs6219) were selected, and the genotyping was performed by TaqMan technique. A quantitative trait analysis and stratification analysis were performed for evaluating the relation between IGF-1genetic variation and blood pressure by taking different antihypertensive drugs. RESULTS:Quantitative trait analysis showed that there were significant differences in diastolic blood pressure (DBP) among the genotypes(GG,GA and AA) of rs6219 in hypertensive taking Jiang Ya Tablet after adjusting the covariant (P=0.01). In hypertensive taking compound reserpine, rs5742612 T/C and rs6218 T/C were significantly associated with systolic blood pressure（SBP）after adjustment for covariates, P values of 0.04 and 0.017, respectively. In hypertensive taking Zhenju Jiang Ya Table, after adjusting the covariant, the variation of rs6218 significantly related to DBP, and the variation of rs6219 was associated with SBP(The P values were 0.017 and 0.033, respectively).Further stratification analysis indicated that in female hypertensive taking Jiang Ya Tablet, SBP significantly decreased with the variation (T>C) of rs37567 (P=0.028). Interestingly, in male hypertensive taking Jiang Ya Tablet, DBP significantly increased with the variation of rs37567 (P=0.038). CONCLUSION: IGF-1 gene polymorphism is significantly related to efficacy of antihypertensive drugs including compound reserpine, Jiang Ya Tablet and Zhenju Jiang Ya Tablet, and may serve as a useful biomarker for the treatment of hypertension and gene therapy.

Key words: insulin-like growth factor (IGF)-1, gene polymorphisms, antihypertensive drugs, blood pressure

中图分类号:

R544

陈燕，朱丽君，方正美，朱汇，金岳龙，沈冲，姚应水. 胰岛素样生长因子1基因多态性与常用抗高血压药物治疗后血压水平的关联研究[J]. 中国临床药理学与治疗学, 2019, 24(2): 171-179.

CHEN Yan, ZHU Lijun, FANG Zhengmei, ZHU Hui, JIN Yuelong, SHEN Chong, YAO Yingshui. Association of insulin-like growth factor(IGF)-1 polymorphisms and efficacy of antihypertensive drugs[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(2): 171-179.

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胰岛素样生长因子1基因多态性与常用抗高血压药物治疗后血压水平的关联研究

Association of insulin-like growth factor(IGF)-1 polymorphisms and efficacy of antihypertensive drugs

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