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Cholesteryl ester transfer protein polymorphism D442G associated with a potential decreased risk for Alzheimer's disease as a modifier for APOE epsilon4 in Chinese.

Abstract

There is compelling evidence indicating that reduction of high-density lipoprotein (HDL) level is associated with increased risk of Alzheimer's disease (AD). It is known that the levels of HDL are regulated by cholesteryl ester transfer protein (CETP) and several single nucleotide polymorphisms (SNPs) in the CETP gene have been shown to be associated with the levels of HDL. Therefore, it is assumed that the CETP gene is a reasonable candidate for modifying the susceptibility in AD. In the present study, we investigated the association of four CETP SNPs (D442G, L296Q, Taq1B and I405V) with the risk for sporadic AD in Northern Han-Chinese. One hundred and seven AD cases and 115 age and gender-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. The frequency of DG genotype (P=0.035) or G allele (P=0.038) for the CETP (D442G) polymorphism was greater in control subjects than in AD patients. The age- and sex-adjusted odds radio for DG vs. DD genotype was 0.202 (95% CI 0.043-0.958, P=0.044). When the sample was stratified by APOE epsilon4 carrier status, the same tendency (P=0.042 for DG genotype, P=0.046 for G allele) was observed in the presence of APOE epsilon4, but not in the absence of APOE epsilon4 (P=0.284 for DG genotype, P=0.298 for G allele). However, these results became not statistically significant after correcting for multiple testing (Bonferroni) because of limited number of our sample. Our current results suggest that G allele of CETP D442G may have a potential protective effect against the development of AD, especially in APOE epsilon4 carriers, in Northern Han-Chinese, possibly through regulating the HDL level in the brain.

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  • Authors+Show Affiliations

    ,

    Beijing Institute of Geriatrics and Department of Neurobiology and Neurology, Xuanwu Hospital of Capital Medical University, #45 Changchun Street, Beijing 100053, China.

    , , , , ,

    Source

    Brain research 1187: 2008 Jan 02 pg 52-7

    MeSH

    Age Distribution
    Aged
    Aged, 80 and over
    Alzheimer Disease
    Apolipoprotein E4
    Asian Continental Ancestry Group
    Cholesterol Ester Transfer Proteins
    DNA Mutational Analysis
    Female
    Gene Frequency
    Genetic Markers
    Genetic Predisposition to Disease
    Genetic Testing
    Genotype
    Heterozygote
    Humans
    Lipoproteins, HDL
    Male
    Polymorphism, Genetic
    Sex Distribution

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    18036514

    Citation

    Chen, Da-Wei, et al. "Cholesteryl Ester Transfer Protein Polymorphism D442G Associated With a Potential Decreased Risk for Alzheimer's Disease as a Modifier for APOE Epsilon4 in Chinese." Brain Research, vol. 1187, 2008, pp. 52-7.
    Chen DW, Yang JF, Tang Z, et al. Cholesteryl ester transfer protein polymorphism D442G associated with a potential decreased risk for Alzheimer's disease as a modifier for APOE epsilon4 in Chinese. Brain Res. 2008;1187:52-7.
    Chen, D. W., Yang, J. F., Tang, Z., Dong, X. M., Feng, X. L., Yu, S., & Chan, P. (2008). Cholesteryl ester transfer protein polymorphism D442G associated with a potential decreased risk for Alzheimer's disease as a modifier for APOE epsilon4 in Chinese. Brain Research, 1187, pp. 52-7.
    Chen DW, et al. Cholesteryl Ester Transfer Protein Polymorphism D442G Associated With a Potential Decreased Risk for Alzheimer's Disease as a Modifier for APOE Epsilon4 in Chinese. Brain Res. 2008 Jan 2;1187:52-7. PubMed PMID: 18036514.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cholesteryl ester transfer protein polymorphism D442G associated with a potential decreased risk for Alzheimer's disease as a modifier for APOE epsilon4 in Chinese. AU - Chen,Da-Wei, AU - Yang,Jing-Fang, AU - Tang,Zhe, AU - Dong,Xiu-Min, AU - Feng,Xiu-Li, AU - Yu,Shun, AU - Chan,Piu, Y1 - 2007/11/26/ PY - 2007/06/23/received PY - 2007/10/07/revised PY - 2007/10/16/accepted PY - 2007/11/27/pubmed PY - 2008/3/18/medline PY - 2007/11/27/entrez SP - 52 EP - 7 JF - Brain research JO - Brain Res. VL - 1187 N2 - There is compelling evidence indicating that reduction of high-density lipoprotein (HDL) level is associated with increased risk of Alzheimer's disease (AD). It is known that the levels of HDL are regulated by cholesteryl ester transfer protein (CETP) and several single nucleotide polymorphisms (SNPs) in the CETP gene have been shown to be associated with the levels of HDL. Therefore, it is assumed that the CETP gene is a reasonable candidate for modifying the susceptibility in AD. In the present study, we investigated the association of four CETP SNPs (D442G, L296Q, Taq1B and I405V) with the risk for sporadic AD in Northern Han-Chinese. One hundred and seven AD cases and 115 age and gender-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. The frequency of DG genotype (P=0.035) or G allele (P=0.038) for the CETP (D442G) polymorphism was greater in control subjects than in AD patients. The age- and sex-adjusted odds radio for DG vs. DD genotype was 0.202 (95% CI 0.043-0.958, P=0.044). When the sample was stratified by APOE epsilon4 carrier status, the same tendency (P=0.042 for DG genotype, P=0.046 for G allele) was observed in the presence of APOE epsilon4, but not in the absence of APOE epsilon4 (P=0.284 for DG genotype, P=0.298 for G allele). However, these results became not statistically significant after correcting for multiple testing (Bonferroni) because of limited number of our sample. Our current results suggest that G allele of CETP D442G may have a potential protective effect against the development of AD, especially in APOE epsilon4 carriers, in Northern Han-Chinese, possibly through regulating the HDL level in the brain. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/18036514/Cholesteryl_ester_transfer_protein_polymorphism_D442G_associated_with_a_potential_decreased_risk_for_Alzheimer's_disease_as_a_modifier_for_APOE_epsilon4_in_Chinese_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(07)02482-1 DB - PRIME DP - Unbound Medicine ER -