吸烟导致的芳香烃受体抑制因子基因低甲基化与冠心病患者死亡风险的相关性  

Relationship between hypomethylation of AHRR gene caused by smoking and the risk of death in pa⁃tients with coronary heart disease

作　　者：汪静 田晓雪 陈爽 吴栋丽 陈纪言 钟诗龙 WANG Jing;TIAN Xiao-xue;CHEN Shuang;WU Dong-li;CHEN Ji-yan;ZHONG Shi-long(School of Biology and Biological Engineering,South China University of Technology,Guangzhou 510006,China;Department of Pharmacy,Guangdong Provincial People′s Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,China;Department of Medical Research,Guangdong Provincial Key Laborato-ry of Coronary Heart Disease Prevention,Guangdong Cardiovascular Institute,Guangdong Provincial People′s Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,China)

机构地区：[1]华南理工大学生物科学与工程学院,广州510006 [2]广东省人民医院(广东省医学科学院)药学部,广州510080 [3]广东省人民医院(广东省医学科学院)医学研究部,广东省冠心病防治研究重点实验室,广州510080

出　　处：《岭南心血管病杂志》2022年第1期1-6,共6页South China Journal of Cardiovascular Diseases

基　　金：广东省重点领域研发计划“精准医学与干细胞”重大科技专项(项目编号:2019B020229003);国家自然科学基金面上项目(项目编号:81872934、81673514);广东省冠心病防治研究重点实验室/基金号(项目编号:2017B0303314041);高层次人才团队建设项目(院内编号:Y012016025、Y012018085)。

摘　　要：目的通过检测冠状动脉粥样硬化性心脏病(冠心病)患者芳香烃受体抑制因子(aryl-hydrocarbon receptor repressor,AHRR)(cg05575921)甲基化水平,探究AHRR基因甲基化水平与吸烟、冠心病患者心血管危险因素及死亡之间的关系。方法于2010至2013年在广东省人民医院心内科入选冠心病患者,172例死亡患者作为死亡组,209例非死亡患者作为对照组。建立焦磷酸测序法检测AHRR(cg05575921)的甲基化水平,验证吸烟与AHRR(cg05575921)甲基化水平的关系,采用线性回归分析对AHRR(cg05575921)甲基化与心肌酶、血脂和心功能的相关性进行分析,采用Logistic回归分析对AHRR(cg05575921)甲基化水平与冠心病患者全因性死亡的相关性进行分析。结果吸烟患者AHRR(cg05575921)甲基化水平显著低于戒烟患者和不吸烟患者,差异有统计学意义(P<0.0001);戒烟患者AHRR(cg05575921)甲基化水平低于不吸烟患者,差异有统计学意义(P=0.0027)。AHRR(cg05575921)甲基化水平与心肌损伤标志物[丙氨酸氨基转移酶(ALT)、肌酸激酶同工酶(CKMB)、乳酸脱氢酶(LDH)和α-羟丁酸脱氢酶(HBDH)]和左心室收缩末期内径(left ventricular end-systolicdiameter,LVESD)呈显著负相关(P<0.005),与左心室射血分数呈显著正相关(P<0.005)。死亡患者AHRR(cg05575921)甲基化水平显著低于非死亡患者(0.6963±0.0088 vs.0.7224±0.0081,P=0.0064)。校正潜在混杂因素之后,AHRR(cg05575921)甲基化水平与死亡呈显著的负相关(OR=0.046,95%CI:0.0028~0.48965,P=0.0441)。结论吸烟导致AHRR(cg05575921)低甲基化,可能引起冠心病患者的心肌损伤指标升高并且影响心功能,从而增加冠心病患者死亡风险。Objectives To detect the level of aryl-hydrocarbon receptor repressor(AHRR)(cg05575921)methyla⁃tion in patients with coronary heart disease(CAD),and to analyze the relationship between AHRR methylation level and smoking,cardiovascular risk factors and death in patients with CAD.Methods Patients with CAD diagnosed in the Department of Cardiology of Guangdong Provincial People′s Hospital from 2010 to 2013 were selected in this study.Totally 172 patients who died were regarded as death group,and 209 non-dead patients were selected as survival control group after propensity score matching.The pyrosequencing method was established to detect the methylation level of AHRR(cg05575921).The relationship between smoking and AHRR methylation level was verified.The correlations between AHRR methylation level with myocardial enzymes,blood lipids,and heart function were analyzed by linear regression.The correlations between AHRR(cg05575921)methylation level and all-cause death in patients with CAD were analyzed by Logistic regression.Results The degree of AHRR(cg05575921)methylation of smokers was signifi⁃cantly lower than that of former and never-smokers(P<0.0001),and the methylation level of AHRR(cg05575921)of former was also lower than that of never-smokers(P=0.0027).AHRR(cg05575921)methylation level significantly negatively correlated with alanine aminotransferase(ALT),creatine kinase isoenzyme(CKMB),lactate dehydroge⁃nase(LDH),α-Hydroxybutyrate dehydrogenase(HBDH)and left ventricular end-systolic diameter(LVESD)(P<0.005),and significantly positively correlated with left ventricular ejection fraction(LVEF)(P<0.005).The methylation level of AHRR(cg05575921)in dead patients was significantly lower than that in survival patients(0.6963±0.0088 vs.0.7224±0.0081,P=0.0064).After adjusting for potential confounding factors,AHRR(cg05575921)methylation level significantly negatively correlated with death(OR=0.046,95%CI:0.0028-0.48965,P=0.0441).Conclusions Smoking leads to hypomethylation of the AHRR(cg05575921),which may i

关 键 词：冠状动脉疾病 芳香烃受体抑制因子 甲基化 死亡 吸烟 

分 类 号：R541.4[医药卫生—心血管疾病]