Alvarez R, Alvarez V, Lahoz C H, Martínez C, Peña J, Sánchez J M, Guisasola L M, Salas-Puig J, Morís G, Vidal J A, Ribacoba R, Menes B B, Uría D, Coto E
Laboratorio de Genética Molecular-Instituto Reina Sofía de Investigación Nefrológica, Hospital Central de Asturias, Oviedo, Spain.
J Neurol Neurosurg Psychiatry. 1999 Dec;67(6):733-6. doi: 10.1136/jnnp.67.6.733.
Several lines of evidence suggest that the endothelial constitutive nitric oxide synthase (ecNOS) and angiotensin converting enzyme (ACE) may have a role in Alzheimer's disease. ACE is widely expressed in the brain, and a DNA polymorphism at the ACE gene has been linked to the risk for late onset Alzheimer's disease. Nitric oxide (NO) production by microglial cells, astrocytes, and brain microvessels is enhanced in patients with Alzheimer's disease. There is a growing evidence that NO is involved in neuronal death in Alzheimer's disease, and the oxidative stress caused by NO in the brain could be a pathogenic mechanism in Alzheimer's disease. The objective was to determine if two DNA polymorphisms at the ecNOS and ACE genes that have been linked with different levels of enzyme expression, have some effect on the risk of developing late onset Alzheimer disease.
A total of 400 healthy controls younger than 65 years and 350 patients with Alzheimer's disease (average age 72 years) were genotyped for the ACE and ecNOS polymorphisms. To define a possible role for these polymorphisms in longevity 117 healthy controls older than 85 years were also analysed. Genomic DNA was obtained and amplified by polymerase chain reaction, and genotypes were defined following a previously described procedure. Gene and genotype frequencies between patients and controls were compared statistically.
Gene and genotype frequencies for the ecNOS and ACE polymorphisms did not differ between both groups of healthy controls (<65 years and >85 years). EcNOS gene and genotype frequencies were similar between patients and controls. There was a slight but significantly increased frequency of the ACE-I allele among patients with Alzheimer's disease compared with controls (p=0.03; OR=1.28, 95%CI= 1.04;1.58).
The ACE-I allele was associated with a slightly increased risk of developing late onset Alzheimer's disease.
多项证据表明，内皮型一氧化氮合酶（ecNOS）和血管紧张素转换酶（ACE）可能在阿尔茨海默病中发挥作用。ACE在大脑中广泛表达，ACE基因的一个DNA多态性与晚发型阿尔茨海默病的风险相关。阿尔茨海默病患者中，小胶质细胞、星形胶质细胞和脑微血管产生的一氧化氮（NO）增加。越来越多的证据表明，NO参与了阿尔茨海默病中的神经元死亡，并且大脑中由NO引起的氧化应激可能是阿尔茨海默病的一种致病机制。目的是确定ecNOS和ACE基因上与不同水平酶表达相关的两个DNA多态性是否对晚发型阿尔茨海默病的发病风险有影响。
对400名65岁以下的健康对照者和350名阿尔茨海默病患者（平均年龄72岁）进行ACE和ecNOS多态性基因分型。为了确定这些多态性在长寿中的可能作用，还分析了117名85岁以上的健康对照者。获取基因组DNA并通过聚合酶链反应进行扩增，按照先前描述的程序确定基因型。对患者和对照者之间的基因和基因型频率进行统计学比较。
两组健康对照者（<65岁和>85岁）之间ecNOS和ACE多态性的基因和基因型频率没有差异。患者和对照者之间的ecNOS基因和基因型频率相似。与对照者相比，阿尔茨海默病患者中ACE-I等位基因的频率略有增加，但差异有统计学意义（p = 0.03；OR = 1.28，95%CI = 1.04；1.58）。
ACE-I等位基因与晚发型阿尔茨海默病的发病风险略有增加相关。
