Relationships Between CETP Genetic Polymorphisms and Alzheimer's Disease Risk: A Meta-Analysis

Abstract

This meta-analysis was performed to evaluate the relationships between single-nucleotide polymorphisms in the CETP gene and the risk of Alzheimer's disease (AD). The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched from inception through October 1, 2013, without language restrictions. Nine case-control studies with a total of 2172 AD patients and 8017 healthy controls were involved in this meta-analysis. Two common polymorphisms (rs708272 T>C and rs5882 A>G) in the CETP gene were assessed. Our meta-analysis results showed that CETP rs5882 A>G polymorphism might increase the risk of AD (A allele vs. G allele: odds ratio [OR]=1.11, 95% confidence interval [95% CI]=1.02-1.21, p=0.014; AA+AG vs. GG: OR=1.28, 95% CI=1.07-1.52, p=0.006; AA vs. GG: OR=1.32, 95% CI=1.10-1.70, p=0.003; AA vs. AG: OR=1.25, 95% CI=1.03-1.50, p=0.020; respectively). However, we found no correlations of CETP rs708272 T>C polymorphism with AD risk (all p>0.05). Subgroup analysis by ethnicity suggested positive associations between CETP rs5882 A>G polymorphism and an increased risk of AD among Caucasians (A allele vs. G allele: OR=1.10, 95% CI=1.01-1.21, p=0.014; AA+AG vs. GG: OR=1.34, 95% CI=1.06-1.69, p=0.015; AA vs. GG: OR=1.35, 95% CI=1.07-1.70, p=0.011; respectively), but not among Asians (all p>0.05). No associations were found between CETP rs708272 T>C polymorphism and AD risk among both Asians and Caucasians (all p>0.05). Our findings provide empirical evidence that CETP rs5882 A>G polymorphism may contribute to susceptibility to AD, especially among Caucasians. However, CETP rs708272 T>C polymorphism does not seem to be an important determinant in the pathogenesis of AD.

Disorders of lysosomal acidification—The emerging role of v-ATPase in aging and neurodegenerative disease

“…Consistent with this idea, APOE ε4, but not APOE ε3, in a thiorphan-treated APP mouse model of AD, expands lysosomal compartments, increases Aβ co-localization with lysosomes, and causes learning and memory impairment (Belinson et al, 2008). Cholesterol, the principal lipid carried into neurons by ApoE, and a suspected AD risk factor (Chen et al, 2014a; Chen et al, 2014b), also induces neuronal rab5 activation and endocytic upregulation when administered to animals through a high-fat diet (Braccini et al, 2015). Evidence suggests that membrane cholesterol may also influence v-ATPase function more directly.…”

Polymorphism of lipid exchange genes in some populations of South and East Siberia

“…Studies in Caucasians, Americans of African origin, and Chi nese revealed the GG genotype could also be associated with longevity, reduced risk of the Alzheimer's disease, vascular dementia, and grey matter anomalies in posterior brain in healthy elderly people (Sanders et al, 2010;Yu et al, 2012;Chen et al, 2014;Salminen et al, 2015).…”

Associations of cholesteryl ester transfer protein (CETP) gene variants with pituitary adenoma

“…Some studies were carried out in order to find out if CETP could be associated with Alzheimer's disease (AD) knowing that cholesterol dysregulation is linked with this neurodegenerative disease [23][24][25][26][27][28] . The meta-analysis done by Chen et al has shown that CETP rs5882 polymorphism could be associated with higher susceptibility to AD (especially in Caucasians) but polymorphism rs708272 does not play an important role in the pathogenesis of this neurodegenerative disease 27 .…”

“…It is known that high plasma concentrations of CETP are associated with an increased risk of cardiovascular diseases [15][16][20][21][22] . CETP could also be associated with many diseases such as neurodegenerative diseases [23][24][25][26][27][28] , dementia [24][25][26]28 and cancer 29 .…”