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Cholesteryl ester transfer protein (CETP) polymorphism modifies the Alzheimer's disease risk associated with APOE epsilon4 allele.
J Neurol 2006; 253(2):181-5JN

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.

Authors+Show Affiliations

Neurology Service, University Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -