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预防医学  2017, Vol. 29 Issue (3): 260-263    DOI: 10.19485/j.cnki.issn1007-0931.2017.03.011
  论著 本期目录 | 过刊浏览 | 高级检索 |
邱旭君1,范瑞 2,张莉娜2,郝玲妹1
A study on the association of AGTR1 promoter methylation and essential hypertension
QIU Xu-jun,FAN Rui,ZHANG Li-na,HAO Ling-mei
Clinical Laboratory,The Seventh Hospital of Ningbo,Ningbo,Zhejiang,315202,China
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摘要 目的 研究血管紧张素Ⅱ-1型受体(AGTR1)基因启动子区DNA甲基化水平与原发性高血压(EH)的相关性。方法 选取在宁波市居住3代及以上的35~70岁汉族居民3 000人,分为新发病例组、既往病例组和对照组;按年龄、性别1∶1∶1匹配后有96对(共288人)进入病例对照研究。通过调查问卷、体格检查和实验室检测获取研究对象的基线资料及血生化指标。采用焦磷酸测序法检测AGTR1基因启动子区CpG1~CpG5位点的甲基化水平。采用条件Logistic回归模型对混杂因素进行校正,分析抗高血压药物治疗敏感的CpG位点。结果 三组研究对象的BMI、三酰甘油(TG)、空腹血糖(FPG)、高密度脂蛋白(HDL)、尿酸(UA)水平差异均有统计学意义(P<0.05)。条件Logistic回归分析结果显示,与对照组的CpG1甲基化水平(9.66 ±5.45)%比较,新发病例组(6.74 ±4.32)%(OR= 0.888,95% CI:0.792~0.995)和既往病例组(4.99 ±3.97)%(OR= 0.454,95% CI:0.226~0.913)均偏低,而新发病例组与既往病例组间,未见有差异的CpG位点(均P>0.05)。结论 AGTR1基因CpG1的低甲基化是EH的影响因素,抗高血压药物治疗可能对AGTR1基因DNA甲基化水平无影响。
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关键词 原发性高血压血管紧张素Ⅱ-1型受体启动子区DNA甲基化    
AbstractObjective The purpose of this study was to investigate the association of AGTR1 promoter methylation with the risk of essential hypertension (EH),and to explore whether the methylation levels of AGTR1 were influenced by antihypertensive drug therapy.Methods In the current case-control study,with community population-based multi-stage sampling method,a total of 288 individuals including 96 controls,96 gender- and age-matched incidence essential hypertension(In-EH) patients and 96 gender- and age-matched prevalent essential hypertension(Pre-EH) patients were recruited from Han Chinese families in Ningbo City.The baseline data,blood samples and serum biochemical indexes of participants were obtained through questionnaire,conventional check-up and laboratory detection.Methylation levels of CpGdinucleotides in genepromoter of AGTR1 were measured using bisulfite pyrosequencing.Conditional logistic regression was used to adjust for confounding factors,and find the CpG sites which were sensitive to EH and drug.Results Body mass index,triglycerides,fasting blood glucose,high-density lipoprotein and uric acid among the three groups were significantly different (P<0.05).Conditional logistic regression showed that methylation of CpG1 was significantly lower in both In-EH and Pre-EH than in controls(Controls vs.In-EH): 9.66±5.45 vs.6.74±4.32,OR=0.888,95% CI:0.792-0.995; (Controls vs.Pre-EH): 9.66±5.45 vs.4.99±3.97,OR=0.454,95% CI:0.226-0.913.No significant result was observed between In-EH and Pre-EH(P>0.05).Conclusion Hypomethylation of CpG1 in AGTR1 gene is a risk factor for EH.However,no effect of antihyptensive drug therapy on the changes of DNA methylation levels in AGTR1 was found.
Key wordsEssential hypertension    AGTR1    Promoter    DNA methylation
     出版日期: 2017-11-21
ZTFLH:  R544.1  
通信作者: 2016年度省级公益技术应用研究计划项目(2016C33178);宁波市镇海区社会发展科技项目(2012S1007);宁波市医学科技计划项目(2013A39);宁波市社发攻关项目(2014C50051)   
作者简介: 邱旭君,本科,副主任护师,主要从事慢性病防制工作
邱旭君,范瑞 ,张莉娜,郝玲妹. AGTR1基因启动子区DNA甲基化与原发性高血压的相关性研究[J]. 预防医学, 2017, 29(3): 260-263.
QIU Xu-jun,FAN Rui,ZHANG Li-na,HAO Ling-mei. A study on the association of AGTR1 promoter methylation and essential hypertension. Preventive Medicine, 2017, 29(3): 260-263.
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[1]LIM S S,VOS T,FLAXMAN A D,et al.A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions,1990-2010: a systematic analysis for the Global Burden of Disease Study 2010[J].Lancet,2012,380(9859): 2224-2260.
[2]LI D,LV J,LIU F,et al.Hypertension burden and control in mainland China: Analysis of nationwide data 2003-2012[J].Int J Cardiol,2015,184(1): 637-644.
[3]PEI F,WANG X,YUE R,et al.Differential expression and DNA methylation of angiotensin type 1A receptors in vascular tissues during genetic hypertension development[J].Mol Cell Biochem,2015,402(1-2): 1-8.
[4]BOGDARINA I,HAASE A,LANGLEY-EVANS S,et al. Glucocorticoid effects on the programming of AT1b angiotensin receptor gene methylation and expression in the rat[J].PLoS One,2010,5(2): e9237.
[5]BOGDARINA I,WELHAM S,KING P J,et al.Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension[J].Circ Res,2007,100(4): 520-526.
[6]刘力生.中国高血压防治指南2010[J/OL].中国医学前沿杂志(电子版),2011,3 (5): 42-93.
[7]MIKESKA T,FELSBERG J,HEWITT C A,et al.Analysing DNA methylation using bisulphite pyrosequencing[J].Methods Mol Biol,2011(791): 33-53.
[8]FAN R,MAO S,ZHONG F,et al.Association of AGTR1 Promoter Methylation Levels with Essential Hypertension Risk: A Matched Case-Control Study[J].Cytogenet Genome Res,2015,147(2-3): 95-102.
[9]INAGAMI T.Recent progress in molecular and cell biological studies of angiotensin receptors[J].Curr Opin Nephrol Hypertens,1995,4(1): 47-54.
[10]BOGDARINA I G,KING P J,CLARK A J.Characterization of the angiotensin (AT1b) receptor promoter and its regulation by glucocorticoids[J].J Mol Endocrinol,2009,43(2): 73-80.
[11]吴逸海.社区居民高血压流行现状及其与AGTR1基因DNA 甲基化的关系研究[D].福州:福建医科大学,2015.
[12]CRUDO A,PETROPOULOS S,MOISIADIS V G,et al.Prenatal synthetic glucocorticoid treatment changes DNA methylation states in male organ systems: multigenerational effects[J].Endocrinology,2012,153(7): 3269-3283.
[13]MELAS P A,ROGDAKI M,SBY U,et al.Epigenetic aberrations in leukocytes of patients with schizophrenia: association of global DNA methylation with antipsychotic drug treatment and disease onset[J].The FASEB Journal,2012,26(6): 2712-2718.
[14]POLIDORO S,BROCCOLETTI R,CAMPANELLA G,et al.Effects of bisphosphonate treatment on DNA methylation in osteonecrosis of the jaw[J].Mutation Research/Genetic Toxicology and Environmental Mutagenesis,2013,757(2): 104-113.
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