Genetic analysis of vascular factors in Alzheimer's disease.

Genetic risk factors for Alzheimer's disease (AD) have been extensively examined. Several risk factors for AD are shared with vascular dementia (VaD). We performed genetic case-control studies on polymorphisms of the apolipoprotein E (ApoE) gene, the methylene tetrahydrofolate reductase (MTHFR) gene, and the angiotensin-converting enzyme (ACE) gene. The most acceptable genetic risk factor for the development of AD is the ApoE epsilon-4 (ApoE epsilon4) allele. ApoE promoter polymorphisms have also been reported to be associated with AD. As expected, the ApoE epsilon4 allele had strong association with AD in our samples. The ApoE epsilon4 allele was also estimated as a risk factor for VaD. An ApoE promoter polymorphism (-291T/G) did not show positive association with AD or any other diseases. Common MTHFR phenotypes are thought to genetically regulate blood homocysteine level, which has been associated with AD. We failed to show independent associations between AD and the common MTHFR polymorphisms (C677T and A1298C). A deletion polymorphism at intron 16 of the ACE gene has also been associated with AD. In our study, we found a significant ethnic difference of the genotype distribution, but failed to replicate the positive association between the I allele and AD.