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Abstract
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.
- Received August 29, 2003.
- Accepted in final form December 1, 2003.
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