Genetic association of CYP46 and risk for Alzheimer's disease.
An increasing number of studies suggest that cholesterol plays an important role in regulating beta-amyloid (Abeta) metabolism in Alzheimer's disease (AD). One of the most important mechanisms for the elimination of excess brain cholesterol is its conversion into the 24S-hydroxycholesterol catalyzed by cholesterol 24S-hydroxylase (CYP46). Preliminary evidence indicates that an intron 2 CYP46 T/C gene polymorphismis associated with increased brain Abeta load and higher risk of AD. A case-control study utilizing a clinically well-defined group of 321 sporadic AD patients and 315 control subjects was performed to test this association. Our results indicate that the intron 2 CYP46 C/C genotype may predispose to AD, and this association is independent of the apolipoprotein E genotype.
Neurology Service, Marqués de Valdecilla University Hospital (University of Cantabria), Santander, Spain. combarro@unican.es
Onofre
O
Combarros
Jon
J
Infante
Javier
J
Llorca
José
J
Berciano
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D000072556:Cholesterol 24-Hydroxylase; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000235:genetics*
D001057:Apolipoproteins E; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase