Endothelial nitric oxide synthase exon 7 polymorphism, ischemic cerebrovascular disease, and carotid atheroma
Endothelial nitric oxide synthase exon 7 polymorphism, ischemic cerebrovascular disease, and carotid atheroma
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DOI：
10.1161/01.str.29.9.1908
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发表时间：
1998-09-01
期刊：
影响因子：
8.3
通讯作者：
Powell, JF
中科院分区：
文献类型：
--
作者：
Markus, HS;Ruigrok, Y;Powell, JF
背景和目的：内皮型一氧化氮合酶(ENOS)在正常生理学中的作用表明，它可能是卒中的潜在候选基因。ENOS活性降低可能通过高血压或通过异常血管舒缩反应、促进动脉粥样硬化或增加血小板黏附和聚集而导致卒中风险增加。最近，eNOS基因轴突7(894G-->；T)的一种常见的多态被报道为冠状动脉疾病的强烈危险因素。我们确定它是否也是短暂性脑缺血发作(TIA)和缺血性卒中以及颈动脉粥样硬化的危险因素。方法：我们研究了连续361名因缺血性卒中或TIA就诊于神经内科的白人患者和236名正常白人对照组。所有患者均行头颅CT和/或MR成像及高分辨率颈动脉双功超声检查。结果：病例组和对照组NN基因频率分别为13.0%和15.3%(P=0.44)，N等位基因频率分别为39%和37%(P=0.57)。当仅考虑卒中患者(不包括TIA患者)或仅考虑年龄小于或等于65岁的个体时，脑血管疾病与高血压之间存在高度显著的独立关联(优势比，2.87；95%CI，2.0~4.15；P
Background and Purpose-The role of endothelial nitric oxide synthase (eNOS) in normal physiology suggests that it could be a potential candidate gene for stroke. Reduced eNOS activity could mediate an increased stroke risk through hypertension or independent of hypertension through abnormal vasomotor responses, promoting atherogenesis, or increased platelet adhesion and aggregation. Recently, a common polymorphism in axon 7 of the eNOS gene (894G-->T) has been reported to be a strong risk factor for coronary artery disease. We determined whether it was also a risk factor for transient ischemic attack (TIA) and ischemic stroke and for carotid atheroma.Methods-We studied 361 consecutive white patients presenting with ischemic stroke or TIA to a neurological cerebrovascular disease service and 236 normal white controls. In all patients CT and/or MR head imaging and high-resolution carotid duplex ultrasound were performed. The presence of the polymorphism (N/n) was determined by polymerase chain reaction and restriction with the enzyme BanII.Results-There was no difference in the frequency of the NN genotype between patients and controls (13.0% versus 15.3%; P=0.44) or in N allele frequency (39% versus 37%; P=0.57). There was no association with genotype when only patients with stroke (excluding those with TIA) or when only individuals aged less than or equal to 65 years were considered In contrast, there was a highly significant independent association between cerebrovascular disease and hypertension (odds ratio, 2.87; 95% CI, 2.0 to 4.15; P