Polymorphisms in the CYP19 gene confer increased risk for Alzheimer disease

Background: Brain aromatase may be neuroprotective by increasing the local estrogen levels in injured neurons. Aromatase is encoded by the CYP19 gene located at 15q21.1, a chromosomal region in linkage disequilibrium (LD) with Alzheimer disease (AD) in this sample. Objective: To investigate whether nine single-nucleotide polymorphisms (SNP) spanning the CYP19 gene were associated with AD. Methods: Three hundred ninety-four patients were compared with 469 nondemented control subjects using single-locus and haplotype approaches. Haplotypes were identified using the expectation/maximization algorithm and latent class analysis, which included additional information on age, sex, and APOE polymorphism. Results: Allelic and genotypic frequencies for three adjacent SNP differed between AD and control groups. Both haplotype approaches identified an approximately 60% increase (p=0.02) in the risk of AD for one haplotype and similar levels of excess risk irrespective of APOE polymorphism and gender. Conclusion: Genetic variation in the brain aromatase gene may modify the risk for AD.