Angiotensin converting enzyme and endothelial nitric oxide synthase DNA polymorphisms and late onset Alzheimer's disease

Objectives-Several lines of evidence suggest that the endothelial constitut ive nitric oxide synthase (ecNOS) and angiotensin converting enzyme (ACE) m ay 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 la te onset Alzheimer's disease. Nitric oxide (NO) production by microglial ce lls, astrocytes, and brain microvessels is enhanced in patients with Alzhei mer'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 effe ct on the risk of developing late onset Alzheimer disease. Methods-A total of 400 healthy controls younger than 65 years and 350 patie nts with Alzheimer's disease (average age 72 years) were genotyped for the ACE and ecNOS polymorphisms. To define a possible role for these polymorphi sms in longevity 117 healthy controls older than 85 years were also analyse d. Genomic DNA was obtained and amplified by polymerase chain reaction, and genotypes were defined following a previously described procedure. Gene an d genotype frequencies between patients and controls Results-Gene and genotype frequencies for the ecNOS and ACE polymorphisms d id not differ between both groups of healthy controls (<65 years and >85 ye ars). 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). Conclusions-The ACE-I allele was associated with a slightly increased risk of developing late onset Alzheimer's disease.