Polymorphism Study of Susceptibility Genes Related to Sporadic Alzheimer's Disease

ABSTRACT

Background: We investigated whether any single nucleotide polymorphism of the 7 candidate susceptibility genes is associated with sporadic Alzheimer's disease (AD). Methods: Genomic DNA from brain tissues of registered cases of autopsy-confirmed, sporadic AD (n=45) and from non-demented cerebral infarct with atherosclerosis (A/S, n=36) as a control group were isolated and single strand conformational polymorphism was done. Results: 287 base pair insertion/deletion (I/D) of angiotensin converting enzyme (ACE) was most frequent genotype in AD and infarct- A/S. Among (GT)18, (GT)19 and (GT)20 polymorphism, (GT)18 polymorphism in the promoter region of neprilysin (NEP) was most com- monly found in AD and infarct-A/S. CT genotype of NEP*159C>T in 3'-untranslated region was most frequent genotype in AD and infarct-A/S. ACE genotype and allele both were associated with the frequency of NEP (GT)n genotype (p<0.05) in AD. Polymorphisms of cathepsin D, nitric oxide synthase 3, low density lipoprotein receptor related-protein, G protein beta3-subunit and LBP-1c/CP2/LSF transcriptional factor were not related to AD. Conclusion: Coexistence of ACE I/D and NEP (GT)n polymorphism appeared to be a genetic risk factor for sporadic AD in comparison with cerebral infarct-atherosclerosis.