Genetic polymorphisms in the cathespin D and interleukin-6 genes and the risk of Alzheimer's disease
Genetic polymorphisms in the cathespin D and interleukin-6 genes and the risk of Alzheimer's disease
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DOI：
10.1016/s0304-3940(00)01185-x
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发表时间：
2000-07-07
影响因子：
2.5
通讯作者：
Kamboh, MI
中科院分区：
文献类型：
--
作者：
Bhojak, TJ;DeKosky, ST;Kamboh, MI
阿尔茨海默病(AD)是一种复杂的多因素疾病，涉及多个可能基因。已知的易感基因APOE的载脂蛋白E*4(APOE*4)等位基因既不是引起AD的必要条件，也不是引起AD的充分条件。这促使人们寻找与阿尔茨海默病风险相关的其他候选基因。组织蛋白酶D(Cat D)是一种细胞内天冬氨酸蛋白酶，已被报道在体外具有β和γ分泌酶活性。Cat D基因外显子2存在C->；T(Ala--&Gt；Val)多态已被报道与AD风险增加相关。此外，由于炎症被报道在AD的发病机制中起着重要作用，已知的炎症介质IL-6是另一个被认为与AD风险相关的候选基因。据报道，IL-6基因的遗传变异与AD的风险有关。我们对散发性晚发性AD患者和年龄匹配的对照组进行了基因筛查，以评估Cat D和IL-6基因多态在AD中的作用。我们的数据表明，这些基因多态与AD风险之间没有显著的关联。当数据按APOE*4状态分层时，病例和对照组之间也没有显著差异。这些数据表明，在我们的病例对照队列中，Cat D和IL-6基因多态并不显著改变AD的风险。(C)2000爱思唯尔爱尔兰科学有限公司。保留所有权利。
Alzheimer's disease (AD) is a complex multi-factorial disease with the involvement of several possible genes. The apolipoprotein E*4 (APOE*4) allele of the known susceptibility gene, APOE, is neither necessary,nor sufficient to cause AD. This has prompted the search for other candidate genes associated with the risk of AD. Cathepsin D (Cat D) is an intracellular aspartyl protease that has been reported to have in vitro beta and gamma-secretase activity. The presence of a C --> T (Ala --> Val) polymorphism in exon 2 of the Cat D gene has been reported to be associated with an increased risk of AD. Further, as inflammation is reported to play a prominent role is AD pathogenesis, IL-6, a known mediator of inflammation, is another candidate gene proposed to be associated with the risk of AD. Genetic variation in the IL-6 gene has been reported to be associated with the risk of AD. We performed a genetic screening of sporadic, late-onset AD cases and age-matched controls to evaluate the role of Cat D and IL-6 polymorphisms in AD. Our data indicate no significant association between these polymorphisms and the risk of AD. When the data were stratified by APOE*4 status, no significant difference was seen either between cases and controls. These data suggest that the Cat D and IL-6 polymorphisms do not significantly alter the risk of AD in our case-control cohort. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.