Genetic variation in the cholesterol 24-hydroxylase (CYP46) gene and the risk of Alzheimer's disease.
Alzheimer's disease (AD) is a complex, multifactorial disorder, with many genetic and environmental factors implicated in disease onset and pathology. Increasing evidence points to a link between brain cholesterol turnover and AD. The CYP46 gene encodes for the enzyme, cholesterol 24-hydroxylase, which plays a key role in brain cholesterol turnover. A polymorphism in Intron 2 (T-->C) in the CYP46 gene has recently been reported to be associated with the risk of AD. In the present study, we examined the association of this CYP46 polymorphism with sporadic late-onset AD (LOAD) in American White (434 cases, 401 controls) and African American (54 cases, 61 controls) cohorts. No significant association was observed between the CYP46 polymorphism and LOAD. When the data were stratified by the apolipoprotein E*4 carrier status, no significant difference was observed between cases and controls for the CYP46 single nucleotide polymorphism. In addition, no significant difference in genotype or allele frequency was observed when stratified by the presence or absence of the alpha1-antichymotrypsin*A allele. Our data indicate that the Intron 2 polymorphism of CYP46 does not affect the risk of AD in our sample.
Department of Human Genetics, University of Pittsburgh, 130 Desoto Street, Pittsburgh, PA 15216, USA.
Purnima
P
Desai
Steven T
ST
DeKosky
M Ilyas
MI
Kamboh
D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D044383:Black People / Q000235:genetics; D001921:Brain / Q000201:enzymology* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism*; D000072556:Cholesterol 24-Hydroxylase; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics; D001741:Black or African American
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D002784:Cholesterol; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase