被动吸烟及其与易感基因、抗磷脂抗体交互作用对SLE患者心血管事件的影响

Systemic lupus erythematosus (SLE) is a typical autoimmune disease characterized by the production of autoantibodies and a very high relative risk for cardiovascular events (CVE) which have been the most common cause of death in patients with SLE. Traditional risk factor such as smoking is associated with CVE among patients with SLE. Recently studies also found that smoking have a positive association with SLE pro-thrombotic antiphospholipid antibodies (aPL). Moreover, smoking can synergistically act with several susceptibility genes to increase the risk of cardiovascular diseases in condition of autoimmunity. Given that 90% of affected SLE patients are females and prevalence of smoking in females is relatively low, we hypothesize that passive smoking may have a greater influence on pathogenesis and public health. However, these studies only focus on smoking and the epidemiological evidence of passive smoking is still scarce. In this study, based on established field of the epidemiological investigation, we will collect samples from SLE patients and their related data, and then longitudinal study will be conducted to estimate the role of passive smoking for CVE in patients with SLE. Since these risk factors do not fully account for the high incidence of CVE, we then will explore possible interaction between passive smoking and susceptibility genes, aPL with regard to CVE risk in SLE. Our program might provide new insight into the pathogenesis of cardiovascular diseases in patients with SLE and establish possible prevention and control measures for fatal complication of SLE.

系统性红斑狼疮（SLE）患者发生心血管事件风险远高于一般人群，并已成为其主要死因。传统因素吸烟增加了SLE患者心血管事件风险，且吸烟与SLE抗磷脂抗体产生相关，而后者能诱导血栓形成。此外，吸烟还可与一些易感基因协同作用引起自身免疫病患者发生心血管疾病。鉴于SLE主要累及女性（约占90%），而研究表明女性吸烟率较低，据此推测被动吸烟危害可能更大。但迄今为止，相应的研究仅局限于吸烟，而缺乏被动吸烟的人群证据。为此本项目拟在已建立的流行病学现场基础上，以SLE患者为研究对象，采用纵向研究的方法，收集相关因素调查问卷及采集外周静脉血，探讨SLE患者被动吸烟状况及其与心血管事件的关联。由于独立因素累加不能完全解释全部风险，课题组拟进一步评估被动吸烟与易感基因多态性、抗磷脂抗体交互作用对SLE患者发生心血管事件的影响。本次研究成果对降低SLE致死性并发症的风险具有重要的机制学意义和公共卫生学意义。

系统性红斑狼疮（SLE）患者发生心血管事件风险远高于一般人群，并已成为其主要死因。传统因素吸烟增加了SLE患者心血管事件风险，且吸烟与SLE抗磷脂抗体产生相关，而后者能诱导血栓形成。此外，吸烟还可与一些易感基因协同作用引起自身免疫病患者发生心血管疾病。鉴于SLE主要累及女性（约占90%），而研究表明女性吸烟率较低，据此推测被动吸烟危害可能更大。但迄今为止，相应的研究仅局限于吸烟，而缺乏被动吸烟的人群证据。为此本项目拟在已建立的流行病学现场基础上，以SLE患者为研究对象，收集相关因素调查问卷及采集外周静脉血，探讨SLE患者被动吸烟状况及其与心血管事件的关联。由于独立因素累加不能完全解释全部风险，课题组拟进一步评估被动吸烟与易感基因多态性、抗磷脂抗体交互作用对SLE患者发生心血管事件的影响。结果提示SLE患者中被动吸烟流行率为44.1%。被动吸烟暴露与SLE患者体内多种抗磷脂抗体水平增加和CVE发生有关；亚组分析提示被动吸烟暴露还可能与抗心磷脂抗体-IGG存在交互作用。此外，多因素分析提示SLE患者被动吸烟暴露可能与其并发关节炎、血液学异常等症状显著相关。综上，本项目的数据提示女性SLE人群应远离被动吸烟的环境，从而降低SLE致死性并发症的风险。