The cholesteryl ester transfer protein (CETP) gene and the risk of Alzheimer's disease.
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 OR(VV) = 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.
Arias-Vásquez
Alejandro
A
Department of Epidemiology & Biostatistics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands. a.ariasvasquez@erasmusmc.nl
Isaacs
Aaron
A
Aulchenko
Yurii S
YS
Hofman
Albert
A
Oostra
Ben A
BA
Breteler
Monique
M
van Duijn
Cornelia M
CM
D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D002353:Carrier State; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins