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CYP46 T/C Polymorphism is not Associated with Alzheimer’s Dementia in a Population from Hungary

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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 (χ2=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 ɛ4 allele was significantly over-represented (χ2=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 ɛ4 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 ɛ4 allele) does not increase the susceptibility to late-onset sporadic AD in the Hungarian population.

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Authors and Affiliations

  1. Department of Psychiatry, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, Szeged, Hungary

    Anna Juhász, Ágnes Rimanóczy, Marianna Zana, Annamária Bjelik, Magdolna Pákáski, Nikoletta Bódi, András Palotás, Zoltán Janka & János Kálmán

  2. Department of Medical Informatics, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, Szeged, Hungary

    Krisztina Boda

  3. Department of Psychiatry, “Pándy Kálmán” Municipal Hospital of Békés County, Gyula, Hungary

    Gábor Vincze & Győző Szlávik

  4. Division of Cardiac Surgery Center for Cardiology, Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of Medicine, University of Szeged, H-6720, Pécsi u. 4, Szeged, Hungary

    András Palotás

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  1. Anna Juhász
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Correspondence to András Palotás.

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Juhász, A., Rimanóczy, Á., Boda, K. et al. CYP46 T/C Polymorphism is not Associated with Alzheimer’s Dementia in a Population from Hungary. Neurochem Res 30, 943–948 (2005). https://doi.org/10.1007/s11064-005-5979-4

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