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The cholesteryl ester transfer protein (CETP) gene and the risk of Alzheimer’s disease

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Abstract

Like the apolipoprotein E (APOE) gene, the most common genetic determinant for Alzheimer’s disease (AD), the cholesteryl ester transfer protein (CETP) is involved in lipid metabolism. We studied the I405V polymorphism of the CETP gene in relation to AD. We genotyped 544 AD cases and 5,404 controls from the Rotterdam study, using a TaqMan allelic discrimination assay. Odds ratios (ORs) for AD were estimated using logistic regression analysis. CETP VV carriers showed significantly increased high-density lipoprotein levels compared to the IV and II carriers. In the overall analysis of AD, the risk of disease for the VV carriers of the CETP polymorphism was non-significantly increased compared to II carriers ORVV = 1.33, 95% confidence interval (CI) 0.96–1.90 p = 0.08). In those without the APOE*4 allele, the risk of AD for VV carriers was increased 1.67-fold (95% CI 1.11–2.52, p = 0.01). The difference in the relationship between CETP and AD between APOE*4 carriers and APOE*4 non-carriers was statistically significant (p for interaction = 0.04). Our results suggest that the VV genotype of the I405V polymorphism of the CETP gene increases the risk of AD in the absence of the APOE*4 allele, probably through a cholesterol metabolism pathway in the brain.

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Acknowledgement

A. Arias-Vasquez is supported by a grant from the Centre of Medical Systems Biology, grant no. 297-2003 and the Hersenstichting Nederland. The Rotterdam study is supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The contributions of the general practitioners and pharmacists of the Ommoord district are greatly acknowledged. The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Epidemiology & Biostatistics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

    Alejandro Arias-Vásquez, Aaron Isaacs, Yurii S. Aulchenko, Albert Hofman, Monique Breteler & Cornelia M. van Duijn

  2. Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands

    Ben A. Oostra

  3. Genetic Epidemiology Unit, Department of Epidemiology & Biostatistics, Erasmus Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands

    Alejandro Arias-Vásquez

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  1. Alejandro Arias-Vásquez
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  2. Aaron Isaacs
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Correspondence to Alejandro Arias-Vásquez.

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Arias-Vásquez, A., Isaacs, A., Aulchenko, Y.S. et al. The cholesteryl ester transfer protein (CETP) gene and the risk of Alzheimer’s disease. Neurogenetics 8, 189–193 (2007). https://doi.org/10.1007/s10048-007-0089-x

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  • DOI: https://doi.org/10.1007/s10048-007-0089-x

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