title: Association studies of several cholesterol-related genes (ABCA1, CETP and LIPC) with serum lipids and risk of Alzheimer's disease.
abstract: OBJECTIVE
  Accumulating 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.
  
  
  METHODS
  Case-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.
  
  
  CONCLUSIONS
  We 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.
authors.affiliation: Department of Neurology, The Second XiangYa Hospital of Central South University, No,139 of People's Middle Road, Changsha, Hunan Province 410011, People's Republic of China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Xiao
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Weirong
authors.initials: W
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Houlin
authors.initials: H
authors.lastname: Zeng
authors.forename: Weixi
authors.initials: W
authors.lastname: Chen
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D002681:China; D002784:Cholesterol / Q000097:blood / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008055:Lipids / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; C504173:LIPC protein, human; D008055:Lipids; D002784:Cholesterol; D008049:Lipase