吸烟、F 2RL 3 基因甲基化与稳定性冠状动脉粥样硬化性心脏病预后的关系

Correlations of smoking and F2RL3 gene methylation with prognosis of stable coronary heart disease

摘要:

目的 探讨F 2RL 3 基因甲基化与稳定性冠状动脉粥样硬化性心脏病（简称冠心病）继发心血管事件、死亡率的相关性，及F 2RL 3 基因甲基化与吸烟导致稳定性冠心病患者有害作用的关系。方法 募集南华大学附属第二医院121 例经历过急性冠状动脉综合征、心肌梗死或冠状动脉介入治疗后接受心血管康复计划的住院患者。随访超过8 年。F 2RL 3 基因位点甲基化特点采用Sequenom 基质辅助激光解吸电离时间飞行质谱分析。F 2RL 3 基因甲基化、吸烟与继发性心血管事件、特因和全因死亡率之间的相关性由估计混杂因素控制危险比的多变量Cox 回归模型分析。结果 随访期间，5 例患者发生非致死性心肌梗死，4 例患者发生非致死性脑卒中，6 例患者发生心血管疾病死亡，5 例患者因为其他原因死亡。调整已知预后因素后，Cox 模型分析显示F 2RL 3 基因甲基化与死亡率密切相关。与F 2RL 3 基因甲基化四分位数最高的稳定性冠心病患者相比，四分位最低的患者死于心血管疾病、非心血管疾病或其他任何原因的校正危险比（95%CI）分别为2.32（0.97，5.58）、5.16（1.81，14.7）和3.19（1.64，6.21）。两组患者继发性心血管事件无相关性。将F 2RL 3 纳入回归模型后，吸烟与所有预后结果的相关性减弱。结论 F 2RL 3 甲基化是吸烟有害影响的潜在介导者，并与稳定性冠心病死亡率密切相关。

Abstract:

Objective To determine whether methylation of F2RL3 gene is associated with secondary cardiovascular events and mortality of stable coronary heart disease and with the harmful effect of smoking.Methods A total of 121 inpatients participating cardiovascular rehabilitation programmes after experiencing acute coronary syndrome, myocardial infarction or coronary intervention were recruited in our hospital. Active followup was conducted over 8 years. Methylation of F2RL3 gene was characterized by Sequenom matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Associations of methylation of F2RL3 gene and smoking with secondary cardiovascular events, and specific-cause and all-cause mortality were examined by multiple Cox’s regression model through estimating confounder-controlled hazard ratios. Results During the follow-up, 5 patients suffered from non-fatal myocardial infarction, 4 had non-fatal strokes, 6 died of cardiovascular diseases, and 5 died due to other causes. After controlling established prognostic factors, Cox’s regression analysis revealed F2RL3 methylation was closely associated with mortality. Adjusted hazard ratios (95% CI) for death from cardiovascular, non-cardiovascular, and any other cause were 2.32 (0.97, 5.58), 5.16 (1.81, 14.7), and 3.19 (1.64, 6.21) in the subjects with the lowest quartile of methylation of F2RL3 gene in comparison to those with the highest quartile. There was no association between the secondary cardiovascular event outcomes of the two groups. The strong associations of smoking with all outcomes were markedly weakened when F2RL3 was included in the regression models. Conclusions The results seem to indicate methylation of F2RL3 is a potential mediator of the detrimental impact of smoking and is strongly related to mortality of patients with stable coronary heart disease.