Tags

Type your tag names separated by a space and hit enter

Cholesteryl ester transfer protein (CETP) polymorphism modifies the Alzheimer's disease risk associated with APOE epsilon4 allele.

Abstract

Cholesterol regulates the production of amyloid beta (Abeta), which is central to the pathogenesis of Alzheimer's disease (AD), with high cellular cholesterol promoting and low cellular cholesterol reducing Abeta in vitro and in vivo. High density lipoprotein (HDL) plays a central role in the removal of excess cholesterol from cells, and cholesteryl ester transfer protein (CETP) is a crucial protein involved in the regulation of HDL levels. Two common polymorphisms in the promoter region (C-629A) and exon 14 I405V of the CETP gene are associated with CETP activity and HDL levels. To investigate if these sequence variants in CETP might be of importance in mediating susceptibility to AD, independently or in concert with apolipoprotein E (APOE) epsilon4 allele, we studied a sample of 286 Spanish AD patients and 315 healthy controls. In APOE epsilon4 carriers, homozygous for the CETP (-629) A allele had approximately a three times lower risk of developing AD (odds ratio 2.33, 95% CI 1.01-5.37), than homozygous and heterozygous carriers of the CETP (-629) C allele (odds ratio 7.12, 95% CI 4.51-11.24, P for APOE epsilon4/CETP (-629) AA genotype interaction < 0.001). Our data suggest that CETP behaves as a modifier gene of the AD risk associated with the APOE epsilon4 allele, possibly through modulation of brain cholesterol metabolism.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Neurology Service, University Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain.

    , , , ,

    Source

    Journal of neurology 253:2 2006 Feb pg 181-5

    MeSH

    Aged
    Aged, 80 and over
    Alleles
    Alzheimer Disease
    Apolipoprotein E4
    Apolipoproteins E
    Carrier Proteins
    Cholesterol Ester Transfer Proteins
    Confidence Intervals
    DNA Mutational Analysis
    Exons
    Female
    Gene Frequency
    Genetic Predisposition to Disease
    Genotype
    Glycoproteins
    Humans
    Isoleucine
    Male
    Middle Aged
    Odds Ratio
    Polymorphism, Genetic
    Promoter Regions, Genetic
    Retrospective Studies
    Risk Factors
    Spain
    Valine

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    16096813

    Citation

    Rodríguez, E, et al. "Cholesteryl Ester Transfer Protein (CETP) Polymorphism Modifies the Alzheimer's Disease Risk Associated With APOE Epsilon4 Allele." Journal of Neurology, vol. 253, no. 2, 2006, pp. 181-5.
    Rodríguez E, Mateo I, Infante J, et al. Cholesteryl ester transfer protein (CETP) polymorphism modifies the Alzheimer's disease risk associated with APOE epsilon4 allele. J Neurol. 2006;253(2):181-5.
    Rodríguez, E., Mateo, I., Infante, J., Llorca, J., Berciano, J., & Combarros, O. (2006). Cholesteryl ester transfer protein (CETP) polymorphism modifies the Alzheimer's disease risk associated with APOE epsilon4 allele. Journal of Neurology, 253(2), pp. 181-5.
    Rodríguez E, et al. Cholesteryl Ester Transfer Protein (CETP) Polymorphism Modifies the Alzheimer's Disease Risk Associated With APOE Epsilon4 Allele. J Neurol. 2006;253(2):181-5. PubMed PMID: 16096813.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cholesteryl ester transfer protein (CETP) polymorphism modifies the Alzheimer's disease risk associated with APOE epsilon4 allele. AU - Rodríguez,E, AU - Mateo,I, AU - Infante,J, AU - Llorca,J, AU - Berciano,J, AU - Combarros,O, Y1 - 2005/08/17/ PY - 2005/02/28/received PY - 2005/05/23/accepted PY - 2005/03/18/revised PY - 2005/8/13/pubmed PY - 2006/6/29/medline PY - 2005/8/13/entrez SP - 181 EP - 5 JF - Journal of neurology JO - J. Neurol. VL - 253 IS - 2 N2 - Cholesterol regulates the production of amyloid beta (Abeta), which is central to the pathogenesis of Alzheimer's disease (AD), with high cellular cholesterol promoting and low cellular cholesterol reducing Abeta in vitro and in vivo. High density lipoprotein (HDL) plays a central role in the removal of excess cholesterol from cells, and cholesteryl ester transfer protein (CETP) is a crucial protein involved in the regulation of HDL levels. Two common polymorphisms in the promoter region (C-629A) and exon 14 I405V of the CETP gene are associated with CETP activity and HDL levels. To investigate if these sequence variants in CETP might be of importance in mediating susceptibility to AD, independently or in concert with apolipoprotein E (APOE) epsilon4 allele, we studied a sample of 286 Spanish AD patients and 315 healthy controls. In APOE epsilon4 carriers, homozygous for the CETP (-629) A allele had approximately a three times lower risk of developing AD (odds ratio 2.33, 95% CI 1.01-5.37), than homozygous and heterozygous carriers of the CETP (-629) C allele (odds ratio 7.12, 95% CI 4.51-11.24, P for APOE epsilon4/CETP (-629) AA genotype interaction < 0.001). Our data suggest that CETP behaves as a modifier gene of the AD risk associated with the APOE epsilon4 allele, possibly through modulation of brain cholesterol metabolism. SN - 0340-5354 UR - https://www.unboundmedicine.com/medline/citation/16096813/Cholesteryl_ester_transfer_protein__CETP__polymorphism_modifies_the_Alzheimer's_disease_risk_associated_with_APOE_epsilon4_allele_ L2 - https://dx.doi.org/10.1007/s00415-005-0945-2 DB - PRIME DP - Unbound Medicine ER -