Deficiency of CARD8 Is Associated with Increased Alzheimer's Disease Risk in Women

被引:27
作者
Fontalba, Ana [2 ]
Gutierrez, Olga [2 ]
Llorca, Javier [3 ,4 ]
Mateo, Ignacio [1 ,5 ]
Berciano, Jose [1 ,5 ]
Luis Fernandez-Luna, Jose [2 ]
Combarros, Onofre [1 ,5 ]
机构
[1] Univ Cantabria, Univ Hosp Marques de Valdecilla, Neurol Serv, ES-39008 Santander, Spain
[2] Univ Cantabria, Univ Hosp Marques de Valdecilla, Sch Med, Unidad Genet Mol, ES-39008 Santander, Spain
[3] Univ Cantabria, Div Epidemiol & Computat Biol, Sch Med, ES-39008 Santander, Spain
[4] Univ Cantabria, CIBERESP, Sch Med, ES-39008 Santander, Spain
[5] Univ Cantabria, Univ Hosp Marques de Valdecilla, CIBERNED, ES-39008 Santander, Spain
关键词
Alzheimer's disease; CARD8; NF-kappa B; ApoE epsilon 4; Polymorphism;
D O I
10.1159/000160956
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
NF-kappa B, a major transcription factor controlling inflammation, is activated in Alzheimer's disease (AD) brains. CARD8 protein has been implicated in the suppression of NF-kappa B activity, but a truncating polymorphism (p.C10X, rs2043211) renders a non-functional CARD8 protein that gives rise to a more active NF-kappa B and an amplification of the inflammatory process. Apolipoprotein E (ApoE) epsilon 4 allele, the major genetic risk factor of AD, is associated with hyperactivation of NF-kappa B and enhanced brain inflammation. In a case-control study in 300 AD patients and 300 healthy controls, we examined whether the CARD8 (p.C10X) polymorphism, independently or in concert with the ApoE epsilon 4 allele, might predispose to AD. Women, but not men, carrying the CARD8 AA genotype (truncated protein) had a 2.39-fold higher risk of developing AD than subjects with the CARD8 TT genotype (full-length protein). This association with susceptibility to AD was independent of the ApoE epsilon 4 allele. Copyright (C) 2008 S. Karger AG, Basel
引用
收藏
页码:247 / 250
页数:4
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