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细胞色素P4502E1和NAD(P)H:醌氧化还原酶1基因多态性与大动脉粥样硬化性缺血性卒中易感性的关联:土耳其人群的病例对照研究

Association of cytochrome P4502E1 and NAD(P)H:quinone oxidoreductase 1 genetic polymorphisms with susceptibility to large artery atherosclerotic ischemic stroke: a case-control study in the Turkish population.

作者信息

Türkanoğlu Özçelik Aysun, Can Demirdöğen Birsen, Demirkaya Şeref, Adalı Orhan

机构信息

Department of Molecular Biology and Genetics, Joint Graduate Program in Biochemistry, Middle East Technical University, 06800, Ankara, Turkey.

Food Safety and Agricultural Research Center, Akdeniz University, Antalya, Turkey.

出版信息

Neurol Sci. 2017 Jun;38(6):1077-1085. doi: 10.1007/s10072-017-2930-9. Epub 2017 Mar 29.

Abstract

Stroke, a major cause of death and disability, is described as interruption or severe reduction of blood flow in cerebral arteries. Oxidative stress plays an important role in the pathogenesis of atherosclerosis and carotid atherosclerosis is a risk factor for stroke. Combination of multiple environmental and genetic risk factors is thought to increase stroke. Therefore, investigation of the polymorphisms of enzymes is of crucial importance to determine the molecular etiology of the disease. To test this hypothesis, we performed a case-control study in which we compared the distribution of CYP2E1 and NQO1 genotypes between 245 large artery atherosclerotic ischemic stroke patients and 145 controls, using PCR-RFLP. A significant difference was observed between stroke patients and controls with respect to the CYP2E15B genotype (odds ratio; OR 8.069, P = 0.011) and allele (OR 7.876, P = 0.011) distribution. However, this polymorphism was not a significant predictor of disease status in logistic regression analysis. NQO12 polymorphism genotype distribution was significantly different between patients and controls (P = 0.027) and heterozygote 12 genotype was found to be a protective factor against large artery atherosclerotic ischemic stroke in logistic regression analysis (OR 0.562, P = 0.018). This is the first study conducted regarding the association of CYP2E1 and NQO1 genetic polymorphisms and large artery atherosclerotic ischemic stroke risk in Turkish population.

摘要

中风是导致死亡和残疾的主要原因,被描述为脑动脉血流中断或严重减少。氧化应激在动脉粥样硬化的发病机制中起重要作用,而颈动脉粥样硬化是中风的一个危险因素。多种环境和遗传风险因素的组合被认为会增加中风的发生几率。因此,研究酶的多态性对于确定该疾病的分子病因至关重要。为了验证这一假设,我们进行了一项病例对照研究,使用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,比较了245例大动脉粥样硬化性缺血性中风患者和145例对照者之间CYP2E1和NQO1基因的分布情况。在中风患者和对照者之间,观察到CYP2E15B基因型(优势比;OR 8.069,P = 0.011)和等位基因(OR 7.876,P = 0.011)的分布存在显著差异。然而,在逻辑回归分析中,这种多态性并不是疾病状态的显著预测指标。NQO12多态性基因型分布在患者和对照者之间存在显著差异(P = 0.027),并且在逻辑回归分析中发现杂合子12基因型是预防大动脉粥样硬化性缺血性中风的一个保护因素(OR 0.562,P = 0.018)。这是第一项关于土耳其人群中CYP2E1和NQO1基因多态性与大动脉粥样硬化性缺血性中风风险之间关联的研究。

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