title: CYP46: a risk factor for Alzheimer's disease or a coincidence?
abstract: Excess cholesterol is removed from the brain via hydroxylation mediated by cholesterol 24S-hydroxylase (CYP46). Although serum and cerebrospinal fluid (CSF) concentrations of 24S-hydroxycholesterol are altered during the progress of Alzheimer's disease, studies carried out to date in different populations on the association of CYP46 gene polymorphisms and risk of AD have been inconclusive. In this report, we analyzed CYP46 polymorphisms in 215 Polish AD cases and 173 healthy individuals. A fragment of CYP46 intron 2 was amplified by PCR reaction and sequenced. We discovered a new single nucleotide substitution in CYP46 intron 2, but found no difference in particular genotype or allele frequencies between AD patients and controls. However, the GG genotype of the known rs754203 polymorphic site might be a risk factor for AD, especially in APOE varepsilon4 carriers. Interestingly, in AD patients the rs754203 G allele was more frequent in males than in females. However, considering the extreme divergence of results obtained by different authors, a clear connection between the CYP46 gene and AD is questionable.
authors.affiliation: Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Poland. golanska@wp.pl
authors.forename: Ewa
authors.initials: E
authors.lastname: Golanska
authors.forename: Krystyna
authors.initials: K
authors.lastname: Hulas-Bigoszewska
authors.forename: Izabela
authors.initials: I
authors.lastname: Wojcik
authors.forename: Piotr
authors.initials: P
authors.lastname: Rieske
authors.forename: Maria
authors.initials: M
authors.lastname: Styczynska
authors.forename: Beata
authors.initials: B
authors.lastname: Peplonska
authors.forename: Anna
authors.initials: A
authors.lastname: Pfeffer
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Luczywek
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Wasiak
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gabryelewicz
authors.forename: Dorota
authors.initials: D
authors.lastname: Religa
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Chodakowska-Zebrowska
authors.forename: Maria
authors.initials: M
authors.lastname: Barcikowska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sobow
authors.forename: Pawel P
authors.initials: PP
authors.lastname: Liberski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D000072556:Cholesterol 24-Hydroxylase; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012307:Risk Factors; D012737:Sex Factors; D013250:Steroid Hydroxylases / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D012333:RNA, Messenger; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase