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NADPH氧化酶基因多态性与7年随访中的死亡率和心血管事件相关。

NADPH Oxidase Gene Polymorphism is Associated with Mortality and Cardiovascular Events in 7-Year Follow-Up.

作者信息

Racis Milena, Sobiczewski Wojciech, Stanisławska-Sachadyn Anna, Wirtwein Marcin, Bluj Elżbieta, Nedoszytko Michał, Borzyszkowska Joanna, Limon Janusz, Rynkiewicz Andrzej, Gruchała Marcin

机构信息

First Department of Cardiology, Medical University of Gdańsk, ul. Dębinki 7, 80-211 Gdańsk, Poland.

Department of Biology and Genetics, Medical University of Gdańsk, ul. Dębinki 1, 80-211 Gdańsk, Poland.

出版信息

J Clin Med. 2020 May 14;9(5):1475. doi: 10.3390/jcm9051475.

Abstract

The gene encodes the regulatory subunit of NADPH oxidase, which maintains the redox state within cells and in the blood vessels. That led us to investigate the course of coronary artery disease (CAD) with regards to polymorphisms. Thus, we recruited 1197 subjects with coronary atherosclerosis and observed them during 7-year follow-up. Three polymorphisms: c.214C>T (rs4673), c.-932G>A (rs9932581), and c.*24G>A (1049255) were studied for an association with death, major adverse cardiovascular events (MACE) and an elective percutaneous coronary intervention or coronary artery bypass grafting (PCI/CABG). We found an association between the c.214C>T polymorphism and two end points: death and PCI/CABG. c.214TT genotype was associated with a lower risk of death than C allele (9.5% vs. 21%, < 0.05) and a higher risk of PCI/CABG than C allele (69.3% vs. 51.7%, < 0.01). This suggests that the c.214TT genotype may be a protective factor against death OR = 0.47 (95%CI 0.28-0.82; < 0.01), while also being a risk factor for an elective PCI/CABG OR = 2.36 (95%CI 1.15-4.82; < 0.05). Thus, we hypothesize that among patients with coronary atherosclerosis, the c.214TT genotype contributes to atherosclerotic plaque stability by altering the course of CAD towards chronic coronary syndrome, thereby lowering the incidence of fatal CAD-related events.

摘要

该基因编码烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶的调节亚基,其维持细胞内和血管内的氧化还原状态。这促使我们研究冠状动脉疾病(CAD)与多态性的关系。因此,我们招募了1197名患有冠状动脉粥样硬化的受试者,并在7年的随访期间对他们进行观察。研究了三个多态性:c.214C>T(rs4673)、c.-932G>A(rs9932581)和c.*24G>A(1049255)与死亡、主要不良心血管事件(MACE)以及选择性经皮冠状动脉介入治疗或冠状动脉旁路移植术(PCI/CABG)之间的关联。我们发现c.214C>T多态性与两个终点之间存在关联:死亡和PCI/CABG。c.214TT基因型与死亡风险低于C等位基因相关(9.5%对21%,<0.05),且与PCI/CABG风险高于C等位基因相关(69.3%对51.7%,<0.01)。这表明c.214TT基因型可能是预防死亡的保护因素,比值比(OR)=0.47(95%置信区间[CI]0.28 - 0.82;<0.01),同时也是选择性PCI/CABG的风险因素,OR = 2.36(95%CI 1.15 - 4.82;<0.05)。因此,我们推测在冠状动脉粥样硬化患者中,c.214TT基因型通过将CAD病程转变为慢性冠状动脉综合征来促进动脉粥样硬化斑块的稳定性,从而降低致命性CAD相关事件的发生率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a45/7290726/d4eaf435ad04/jcm-09-01475-g001.jpg

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