心力衰竭患者SLC6A2启动子区甲基化状态及与气虚、血瘀证的相关性  

Methylation in Promoter Region of SLC6A2 Gene in Heart Failure Patients and Its Correlation with Qi Deficiency/Blood Stasis Syndrome

作　　者：骆杰伟[1,2] 孟晓嵘[1,2] 黄昉萌[1,2] 胡丹[3] 杨笑[4] 郑星宇[1,2] 魏世超[2] 郭苗苗[2] 吴仕明[3] 陈宏毅[1,2] 

机构地区：[1]福建医科大学省立临床医学院,福州350001 [2]福建省立医院中医科,福州350001 [3]福建中医药大学第二临床医学院,福州350122 [4]福建卫生职业技术学院护理系外科护理学教研室,福州350101

出　　处：《中国中西医结合杂志》2015年第12期1448-1454,共7页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：福建省自然科学基金资助项目(No.2013J01277);福建省中医药科研项目(No.wzsb201317)

摘　　要：目的探讨心力衰竭（简称心衰）患者去甲肾上腺素转运体（NET,SLC6A2）基因启动子区甲基化状态及其与气虚、血瘀证的相关性。方法选择Ⅲ~Ⅳ级心衰患者36例作为心衰组,评估气虚、血瘀证积分,另收集同期来自福建省立医院体检人群中健康老年30名（老年组）及青年30名（青年组）。采用分段焦磷酸测序法检测SLC6A2基因启动子Cp G岛甲基化水平。应用Pearson及Partial相关分析评价心衰患者SLC6A2基因启动子区甲基化状态与气虚、血瘀积分的相关性,应用Logistic回归筛查和调整危险因素。结果单因素方差分析：心衰组SLC6A2基因启动子区总甲基化率（MTI）为（219.72±54.03）%,明显高于老年组[（194.47±34.92）%]及青年组[（161.60±41.11）%],差异均有统计学意义（P〈0.05）,且老年组高于青年组（P〈0.01）。协方差分析：控制BMI、年龄因素后,心衰组总MTI仍高于老年组（P=0.041）,老年组高于青年组（P=0.016）。3组SLC6A2基因启动子总MIT比较,差异有统计学意义（F=16.447,P=0.01）,青年组SLC6A2基因启动子总MTI偏低。Partial相关分析：心衰组总MTI与气虚、血瘀积分均呈正相关（r值分别为0.494,0.419;P〈0.05）。Logistic回归分析：调整混杂因素后,SLC6A2基因启动子总MTI的相对危险度（OR值）为1.038（95%CI：1.006~1.071,P=0.020）。结论 SLC6A2基因启动子区域甲基化异常升高是心衰的危险因素之一,甲基化程度与心衰患者气虚、血瘀证候呈正相关。Objective To explore the methylation status in promoter region of norepinephrine transporter gene（ NET,SLC6A2） in heart failure（ HF） patients and its correlation with qi deficiency/blood stasis syndrome（ QDS /BSS）.Methods Thirty-six patients with heart failure（ NYHA classification Ⅲ to Ⅳ） were recruited in the study（ as the heart failure group） and their scores of QDS / BSS were evaluated. Besides,a healthy elderly group（ 30 cases） and a healthy youth group（ 30 cases） were also set up. They were recruited from Physical Examination Center of Fujian Provincial Hospital. Pyrosequencing was applied to detect the methylation in promoter region of SLC6A2 gene,and the total methylation index（ MTI） of Cp G island was calculated. The correlation between the methylation status in promoter region of SLC6A2 and scores of QDS / BSS was assessed using Pearson and Partial analyses. Risk factors were screened and adjusted using Logistic regression. Results By one-factor analysis of variance,the total MTI in the HF group（ 219. 72% ± 54. 03%） was obviously higher than that in the healthy elderly group（ 194. 47% ± 34. 92%） and the healthy youth group（ 161. 60% ± 41. 11%）（ all P〈0. 05）. Meanwhile,the total MTI was higher in the healthy elderly group than in the healthy youth group（P〈0. 01）. By covariance analysis,after controlling age and BMI,the total MTI was higher in the HF group than in the healthy elderly group（P = 0. 041）,while it was higher in the healthy elderly group than in the healthy youth group（P = 0. 016）. Age was found to play an essential role in affecting MTI of SLC6A2 gene promoter region among the 3 groups（F = 16. 447,P = 0. 01）. The total MTI was quite lower in the healthy youth group. Results ofP artial correlation analysis showed MTI was positively correlated with scores of qi deficiency and blood stasis respectively（r = 0. 494 and 0. 419 respectively,both P〈0. 05）. Logistic regression analysis showed after adjusting confounding fa

关 键 词：心力衰竭 去甲肾上腺素转运体 DNA甲基化 气虚 血瘀 

分 类 号：R259[医药卫生—中西医结合]