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干扰素-γ 功能单核苷酸多态性(+874T/A)与心血管危险因素在冠心病和早期心肌梗死风险中的交互作用。

Interactive effects of interferon-gamma functional single nucleotid polymorphism (+874 T/A) with cardiovascular risk factors in coronary heart disease and early myocardial infarction risk.

机构信息

Department of Medical Genetic, Giresun University Medical Faculty, Giresun, Turkey.

Department of Cardiology, Giresun A. İlhan Özdemir Education Research Hospital, Giresun, Turkey.

出版信息

Mol Biol Rep. 2020 Nov;47(11):8397-8405. doi: 10.1007/s11033-020-05877-7. Epub 2020 Oct 26.

Abstract

Atherosclerosis is an inflammatory disease characterized by extensive lipid accumulation in the artery wall. Throughout the atherosclerotic process, interferon-gamma (IFN-γ), which is an important pro-inflammatory cytokine, plays a central role in atherosclerotic plaque instability and the occurrence of myocardial infarction (MI). In this study, we aimed to investigate the relationship between IFN-γ +874 T/A (rs2430561) polymorphism and coronary heart disease (CHD) as well as its effects on MI and CHD. Three hundred and ninety patients with CHD (229 with MI, 161 without MI) and 233 healthy controls were screened by the amplification refractory mutation system (ARMS) PCR method for IFN-γ +874 T/A polymorphism. For MI risk, early adult age was important risk factors and the risk was increased with IFN-γ +874 T/A polymorphism. IFN-γ T allele was significantly increased in the CHD patients with age≤45 (p = 0.048) and patients with history of MI (p = 0.007). As IFN-γ is an inflammatory cytokine with an emerging role in the atherosclerotic process, it was suggested that inhibition of IFN-γ activity could be a therapeutic strategy to stabilize human atherosclerotic plaque. Our findings support the association between MI risk and IFN-γ +874 T/A polymorphism in the Turkish population, particularly by increasing the level of IFN-γ in young patients, thereby causing rupture of vulnerable plaques in atherosclerotic lesions. Identification of the IFN-γ +874 T/A gene variants as risk factors for early CHD and MI development may be a practical biomarker to guide the MI risk process and determine the ideal therapeutic approach.

摘要

动脉粥样硬化是一种以动脉壁内广泛脂质积累为特征的炎症性疾病。在动脉粥样硬化过程中,干扰素-γ(IFN-γ)作为一种重要的促炎细胞因子,在动脉粥样硬化斑块不稳定和心肌梗死(MI)的发生中发挥着核心作用。在这项研究中,我们旨在研究 IFN-γ+874 T/A(rs2430561)多态性与冠心病(CHD)的关系及其对 MI 和 CHD 的影响。采用扩增受阻突变系统(ARMS)PCR 法对 390 例 CHD 患者(229 例 MI,161 例非 MI)和 233 例健康对照者进行 IFN-γ+874 T/A 多态性筛查。对于 MI 风险,早发成年是重要的危险因素,IFN-γ+874 T/A 多态性会增加风险。在年龄≤45 岁的 CHD 患者(p=0.048)和有 MI 病史的患者(p=0.007)中,IFN-γ T 等位基因明显增加。由于 IFN-γ 是一种在动脉粥样硬化过程中具有新兴作用的炎症细胞因子,因此抑制 IFN-γ 的活性可能是稳定人动脉粥样硬化斑块的一种治疗策略。我们的研究结果支持 MI 风险与土耳其人群 IFN-γ+874 T/A 多态性之间的关联,特别是通过增加年轻患者 IFN-γ 的水平,从而导致动脉粥样硬化病变中脆弱斑块的破裂。将 IFN-γ+874 T/A 基因变异鉴定为早期 CHD 和 MI 发展的危险因素,可能是指导 MI 风险进程和确定理想治疗方法的实用生物标志物。

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