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Cp G1~Cp G5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Cp G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Cp G1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Cp G位点(均P>0.05)。结论 AGTR1基因Cp G1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。
Objective 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 CpGl was significantly lowerin both In - EH and Pre - EH than in controls （ Controls vs. In - EH） ： 9. 66 ± 5. 45 vs. 6. 74 ± 4. 32, = 0. 8 8 8,95% Cl： 0.792 -0.995 ; （Controls vs. Pre - EH） ： 9. 66 ± 5. 45 vs. 4. 99 ± 3. 9 7 , OR=0 .4 5 4 ,9 5% CI= 0 .2 2 6 - 0 .9 1 3 . No significant result was observed between In - EH and Pre - EH （P 〉 0. 05 ） . Conclusion Hypomethylation of CpGl 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.
出处
《预防医学》
2017年第3期260-263,共4页
CHINA PREVENTIVE MEDICINE JOURNAL
基金
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)
