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.


CONCLUSIONS
Genetic variation in the brain aromatase gene may modify the risk for AD.
Iivonen
S
S
Department of Neuroscience and Neurology, University Hospital and University of Kuopio, Finland.
Corder
E
E
Lehtovirta
M
M
Helisalmi
S
S
Mannermaa
A
A
Vepsäläinen
S
S
Hänninen
T
T
Soininen
H
H
Hiltunen
M
M
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D001141:Aromatase / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment
D001057:Apolipoproteins E; D001141:Aromatase