Crawford F C, Freeman M J, Schinka J A, Abdullah L I, Gold M, Hartman R, Krivian K, Morris M D, Richards D, Duara R, Anand R, Mullan M J
Roskamp Institute University of South Florida, Tampa, FL 33613, USA.
Neurology. 2000 Sep 26;55(6):763-8. doi: 10.1212/wnl.55.6.763.
To investigate whether or not a coding polymorphism in the cystatin C gene (CST3) contributes risk for AD.
A case-control genetic association study of a Caucasian dataset of 309 clinic- and community-based cases and 134 community-based controls.
The authors find a signficant interaction between the GG genotype of CST3 and age/age of onset on risk for AD, such that in the over-80 age group the GG genotype contributes two-fold increased risk for the disease. The authors also see a trend toward interaction between APOE epsilon4-carrying genotype and age/age of onset in this dataset, but in the case of APOE the risk decreases with age. Analysis of only the community-based cases versus controls reveals a significant three-way interaction between APOE, CST3 and age/age of onset.
The reduced or absent risk for AD conferred by APOE in older populations has been well reported in the literature, prompting the suggestion that additional genetic risk factors confer risk for later-onset AD. In the author's dataset the opposite effects of APOE and CST3 genotype on risk for AD with increasing age suggest that CST3 is one of the risk factors for later-onset AD. Although the functional significance of this coding polymorphism has not yet been reported, several hypotheses can be proposed as to how variation in an amyloidogenic cysteine protease inhibitor may have pathologic consequences for AD.
研究胱抑素C基因（CST3）中的编码多态性是否会增加患阿尔茨海默病（AD）的风险。
一项针对309例临床和社区病例以及134例社区对照的白种人数据集的病例对照基因关联研究。
作者发现CST3的GG基因型与年龄/发病年龄之间存在显著的相互作用，对AD风险产生影响，即在80岁以上年龄组中，GG基因型使该疾病的风险增加两倍。作者还在该数据集中观察到携带APOEε4的基因型与年龄/发病年龄之间存在相互作用的趋势，但就APOE而言，风险随年龄降低。仅对社区病例与对照进行分析时，发现APOE、CST3和年龄/发病年龄之间存在显著的三向相互作用。
文献中已充分报道了老年人群中APOE降低或消除AD风险的情况，这促使人们提出，可能存在其他遗传风险因素导致晚发型AD。在作者的数据集中，APOE和CST3基因型对AD风险随年龄增长呈现相反的影响，这表明CST3是晚发型AD的风险因素之一。尽管尚未报道这种编码多态性的功能意义，但可以就淀粉样半胱氨酸蛋白酶抑制剂的变异如何对AD产生病理后果提出几种假设。
