Finckh U, von der Kammer H, Velden J, Michel T, Andresen B, Deng A, Zhang J, Müller-Thomsen T, Zuchowski K, Menzer G, Mann U, Papassotiropoulos A, Heun R, Zurdel J, Holst F, Benussi L, Stoppe G, Reiss J, Miserez A R, Staehelin H B, Rebeck G W, Hyman B T, Binetti G, Hock C, Growdon J H, Nitsch R M
Division of Psychiatry Research, University of Zurich, August Forel Str 1, 8008 Zurich, Switzerland.
Arch Neurol. 2000 Nov;57(11):1579-83. doi: 10.1001/archneur.57.11.1579.
To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD).
A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects.
The Alzheimer's Disease Research Unit at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, for the initial study (n = 260). For the independent multicenter study (n = 647), an international consortium that included the Massachusetts Alzheimer's Disease Research Center at the Massachusetts General Hospital, Boston; the Scientific Institute for Research and Patient Care, Brescia, Italy; and Alzheimer's research units at the Universities of Basel and Zurich, Switzerland, and Bonn, Goettingen, and Hamburg, Germany.
Five hundred seventeen patients with AD and 390 control subjects.
Molecular testing of the KspI polymorphisms in the 5' flanking region and exon 1 of CST3 and the apolipoprotein E (APOE) genotype. Mini-Mental State Examination scores for both patients with AD and control subjects.
Homozygosity for haplotype B of CST3 was significantly associated with late-onset AD in both study populations, with an odds ratio of 3.8 (95% confidence interval, 1.56-9.25) in the combined data set; heterozygosity was not associated with an increased risk. The odds ratios for CST3 B/B increased from 2.6 in those younger than 75 years to 8.8 for those aged 75 years and older. The association of CST3 B/B with AD was independent of APOE epsilon4; both genotypes independently reduced disease-free survival.
CST3 is a susceptibility gene for late-onset AD, especially in patients aged 75 years and older. To our knowledge, CST3 B is the first autosomal recessive risk allele in late-onset AD.
确定胱抑素C基因（CST3）是否与晚发型阿尔茨海默病（AD）存在遗传关联。
一项病例对照研究，涉及2个独立的研究群体，包括AD患者以及年龄匹配、认知功能正常的对照受试者。
德国汉堡-埃彭多夫大学医院的阿尔茨海默病研究单位进行初始研究（n = 260）。独立多中心研究（n = 647）由一个国际联盟开展，其中包括波士顿麻省总医院的马萨诸塞州阿尔茨海默病研究中心；意大利布雷西亚的科研与患者护理科学研究所；以及瑞士巴塞尔大学、苏黎世大学和德国波恩大学、哥廷根大学、汉堡大学的阿尔茨海默病研究单位。
517例AD患者和390名对照受试者。
对CST3基因5'侧翼区和外显子1的KspI多态性以及载脂蛋白E（APOE）基因型进行分子检测。AD患者和对照受试者的简易精神状态检查表评分。
在两个研究群体中，CST3基因单倍型B的纯合性均与晚发型AD显著相关，合并数据集中的比值比为3.8（95%置信区间，1.56 - 9.25）；杂合性与风险增加无关。CST3 B/B的比值比从75岁以下人群的2.6增加到75岁及以上人群的8.8。CST3 B/B与AD的关联独立于APOE ε4；两种基因型均独立降低无病生存期。
CST3是晚发型AD的一个易感基因，尤其是在75岁及以上的患者中。据我们所知，CST3 B是晚发型AD中首个常染色体隐性风险等位基因。
