title: CYP46 T/C polymorphism is not associated with Alzheimer's dementia in a population from Hungary.
abstract: Multiple genetic and environmental factors regulate the susceptibility to Alzheimer's disease (AD). Recently, several independent studies have reported that a locus on chromosome 14q32.1, where a gene encoding a cholesterol degrading enzyme of the brain, called 24-hydroxylase (CYP46A1) is located, has been linked with AD. The single nucleotide polymorphism (T/C) in intron 2 of CYP46 gene has been found to confer the risk for AD. The water soluble 24(S)-hydroxysterol is the product of the CYP46A1, and elevated plasma and cerebrospinal fluid hydroxysterol concentrations have been found in AD, reflecting increased brain cholesterol turnover or cellular degradation, due to the neurodegenerative process. A case-control study was performed on 125 AD and 102 age- and gender-matched control subjects (CNT) from Hungary, to test the association of CYP46 T/C and apolipoprotein E (ApoE) gene polymorphisms in AD. The frequency of the CYP46 C allele was similar (chi2=0.647, df=1, P=0.421, exact P=0.466, OR=0.845; 95% CI: 0.561-1.274) in both groups (CNT: 27%; 95% CI: 21.3-33.4; AD 30%; 95% CI: 25.0-36.3). The ApoE varepsilon4 allele was significantly over-represented (chi2=11.029, df=2, P=0.004) in the AD population (23.2%; 95% CI: 18.2-29.0) when compared with the CNT (11.3%; 95% CI: 7.4-16.6). The presence or absence of one or two CYP46C alleles together with the ApoE varepsilon4 allele did not increase the risk of AD (OR=3.492; 95% CI: 1.401-8.707; P<0.007 and OR=3.714; 95% CI: 1.549-8.908; P<0.003, respectively). Our results indicate that the intron 2 T/C polymorphism of CYP46 gene (neither alone, nor together with the varepsilon4 allele) does not increase the susceptibility to late-onset sporadic AD in the Hungarian population.
authors.affiliation: Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Juhász
authors.forename: Agnes
authors.initials: A
authors.lastname: Rimanóczy
authors.forename: Krisztina
authors.initials: K
authors.lastname: Boda
authors.forename: Gábor
authors.initials: G
authors.lastname: Vincze
authors.forename: Gyozo
authors.initials: G
authors.lastname: Szlávik
authors.forename: Marianna
authors.initials: M
authors.lastname: Zana
authors.forename: Annamária
authors.initials: A
authors.lastname: Bjelik
authors.forename: Magdolna
authors.initials: M
authors.lastname: Pákáski
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Bódi
authors.forename: András
authors.initials: A
authors.lastname: Palotás
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Janka
authors.forename: János
authors.initials: J
authors.lastname: Kálmán
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D000072556:Cholesterol 24-Hydroxylase; D005260:Female; D005828:Genetics, Population; D006801:Humans; D006814:Hungary; D008297:Male; D011110:Polymorphism, Genetic; D013250:Steroid Hydroxylases / Q000235:genetics*
chemical_list: D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase