一氧化氮合酶基因多态性与常用降压药疗效的关联研究

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (5): 538-544.

一氧化氮合酶基因多态性与常用降压药疗效的关联研究

金岳龙¹，王林红¹，朱丽君¹，梁伟¹，段滢¹，杨松³，陈燕春³，赵祥海³，沈冲²，姚应水¹

¹皖南医学院公共卫生学院，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； ³江苏大学附属宜兴市人民医院心血管内科，宜兴 214200，江苏

收稿日期:2017-01-09 修回日期:2017-03-10 出版日期:2017-05-26 发布日期:2017-05-27
通讯作者: 姚应水，男，博士，教授，硕士生导师，研究方向：慢性病分子流行病学。 Tel：13053269969 E-mail：yingshuiyao@163.com
作者简介:金岳龙，男，硕士，副教授，研究方向：慢性病分子流行病学。 Tel：13965178350 E-mail：94017416@qq.com 王林红，女，在读硕士，研究方向：慢性病分子流行病学。 Tel：15150668140 E-mail：943283135@qq.com
基金资助:
国家自然科学基金项目（81072367,81541071,81673266）；安徽高校省级自然科学研究项目（KJ2014A265）；安徽省高校优秀青年人才支持计划（2014年安徽省教育厅）

Association study of NOS3 genetic polymorphism and the efficacy of anti-hypertensive drug treatment on patient with essential hypertension

JIN Yuelong¹, WANG Linhong ¹, ZHU Lijun ¹, LIANG Wei ¹, DUAN Ying¹, YANG Song³, CHEN Yanchun ³, ZHAO Xianghai³, SHEN Chong ², YAO Yingshui ¹

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

Received:2017-01-09 Revised:2017-03-10 Online:2017-05-26 Published:2017-05-27

摘要/Abstract

摘要：

目的:探讨一氧化氮合酶（NOS3)基因的遗传变异对常用降压药物疗效的影响。方法: 收集服用复方利血平、降压片和珍菊降压片的原发性高血压患者一般情况和临床生化指标资料。采用聚合酶链反应(PCR)和限制性片断长度多态性(RFLP)检测NOS3基因上所选3个位点多态性，运用一般线性模型统计方法分析服用不同降压药物后不同基因型间血压水平的变化。结果: 在服用降压片的原发性高血压患者中，rs1808593位点与舒张压的水平呈线性相关，TT基因型的患者舒张压水平高于TG、GG基因型患者，校正协变量后，差异仍有统计学意义（P=0.035）。进一步分层分析显示，在服用降压片的男性原发性高血压患者中，rs1808593位点与舒张压的水平呈线性相关，TT基因型的患者舒张压高于TG、GG基因型患者的舒张压（P=0.046）；同时在服用降压片的≥55岁原发性高血压患者中，rs1808593位点TT基因型的患者舒张压亦高于TG、GG基因型病人的舒张压（P=0.008）。结论:NOS3基因rs1808593突变可能与降压片的降压效果相关。

关键词: NOS3基因, 基因多态性, 原发性高血压, 药物疗效

Abstract:

AIM: To evaluate the effect of NOS3 gene polymorphism on anti-hypertensive drug treatment for patient with essential hypertension (EH). METHODS: General information and Clinical biochemical indicators of EH patients taking compound reserpine, hypertension pill and Zhenju hypertension pill were collected. RELP-PCR was used to test the polymorphism of NOS3 gene (rs4496877, rs1808593 and rs3918186).A quantitative trait analysis was performed to evaluate the relation between NOS3 genetic variation and blood pressure taking different anti-hypertensive drugs. RESULTS: Quantitative trait analysis showed significant differences in diastolic blood pressure (DBP) among the genotypes (TT,TG and GG) of rs1808593 in patients taking the hypertension pill after adjusting covariants (P=0.035). Stratification analysis indicated that DBP of male patients taking the hypertension pill significantly decreased with the variation (T＞G) of rs1808593 (P=0.046). For patients (age≥55) taking the hypertension pill, DBP of genotype TT was significantly higher than genotypes TG and GG of rs1808593(P=0.008). CONCLUSION: NOS3 gene rs1808593 mutation might relate to the anti-hypertensive effect of the hypertension pill.

Key words: NOS3 gene, gene polymorphisms, essential hypertension, drug efficacy

中图分类号:

R968

金岳龙，王林红，朱丽君，梁伟，段滢,杨松，陈燕春，赵祥海，沈冲，姚应水. 一氧化氮合酶基因多态性与常用降压药疗效的关联研究[J]. 中国临床药理学与治疗学, 2017, 22(5): 538-544.

JIN Yuelong, WANG Linhong, ZHU Lijun, LIANG Wei, DUAN Ying, YANG Song, CHEN Yanchun, ZHAO Xianghai, SHEN Chong, YAO Yingshui. Association study of NOS3 genetic polymorphism and the efficacy of anti-hypertensive drug treatment on patient with essential hypertension[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(5): 538-544.

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