Association studies of several cholesterol-related genes (ABCA1, CETP and LIPC) with serum lipids and risk of Alzheimer’s disease

Abstract

ObjectivesAccumulating evidence suggested that dysregulation of cholesterol homeostasis might be a major etiologic factor in initiating and promoting neurodegeneration in Alzheimer’s disease (AD). ATP-binding cassette transporter A1 (ABCA1), hepatic lipase (HL, coding genes named LIPC) and cholesteryl ester transfer protein (CETP) are important components of high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) implicated in atherosclerosis and neurodegenerative diseases. In the present study, we will investigate the possible association of several common polymorphisms (ABCA1R219K, CETPTaqIB and LIPC-250 G/A) with susceptibility to AD and plasma lipid levels.MethodsCase–control study of 208 Han Chinese (104 AD patients and 104 non-demented controls) from Changsha area in Hunan Province was performed using the PCR-RFLP analysis. Cognitive decline was assessed using Mini Mental State Examination (MMSE) as a standardized method. Additionally, fasting lipid profile and the cognitive testing scores including Wechsler Memory Scale (WMS) and Wisconsin Card Sorting Test (WCST) were recorded.Results and conclusionsWe found significant differences among the genotype distributions of these three genes in AD patients when compared with controls. But after adjusting other factors, multivariate logistic regression analysis showed only ABCA1R219K (B = −0.903, P = 0.005, OR = 0.405, 95%CI:0.217-0.758) and LIPC-250 G/A variants(B = −0.905, P = 0.018, OR = 0.405, 95%CI:0.191-0.858) were associated with decreased AD risk. There were significantly higher levels of high-density lipoprotein cholesterol (HDL-C) and apolipoproteinA-I in the carriers of KK genotype and K allele (P < 0.05), and B2B2 genotype of CETP Taq1B showed significant association with higher HDL-C levels than other genotypes (F = 5.598, P = 0.004), while -250 G/A polymorphisms had no significant effect on HDL-C. In total population, subjects carrying ABCA1219K allele or LIPC-250A allele obtained higher MMSE or WMS scores than non-carriers, however, no significant association was observed in AD group or controls. Therefore, this preliminary study showed that the gene variants of ABCA1R219K and LIPC-250 G/A might influence AD susceptibility in South Chinese Han population, but the polymorphism of CETPTaq1B didn't show any association in despite of being a significant determinant of HDL-C.

Serum cholesterol and variant in cholesterol-related gene CETP predict white matter microstructure

“…All SNPs passing the initial inclusion criteria (genotyped with passing MAFs and LDs) were included in keyword searches using Google Scholar to search for prior reports of associations with Alzheimer's disease. Of these, 18 SNPs had been associated with AD, and were included as SNPs of interest in our study (Astarita et al, 2010; Baum et al, 1999; Dzamko, 2011; Gustafsen et al, 2013; Ikeda & Yamada, 2010; Kysenius et al, 2012; Lamsa et al, 2008; Mulder et al, 2012; Natunen et al, 2012; Page et al, 2012; Rodriguez-Rodriguez et al, 2009; Roses et al, 2010; Solfrizzi et al, 2002; Vuletic et al, 2003; Wollmer et al, 2003; Xiao et al, 2012). The SNPs we included are summarized in Table 1.…”

The Epidemiology of Cognitive Impairment in the Aging Population: Implications for Hearing Loss

“…Another key pathological mechanism common for several age-related diseases is represented by lipid dysregulation; numerous studies reported a link between lipids and Alzheimer's disease [Xiao et al, 2012;Mapstone et al, 2014]. In general, membrane lipids provide a milieu for transmembrane proteins and can modulate their function.…”

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

“…In addition, Murphy et al (2012) demonstrated that the V and A alleles of the I405V (rs5882) polymorphism, which lead to increased CETP levels and decreased HDL, were also associated with increased risk of AD. On the other hand, Xiao et al (2012) documented that though the B2B2 genotype of CETP Taq1B (rs708272) showed significant association with higher HDL-C levels than other genotypes (e.g., B1B1 and B1B2), it did not reveal any association with susceptibility to AD due to diverse genotype or allele frequencies in different racial and regional groups.…”