Beyer Katrin, Lao José I, Latorre Pilar, Ariza Aurelio
Department of Pathology, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Barcelona, Spain.
Ann N Y Acad Sci. 2005 Dec;1057:260-78. doi: 10.1196/annals.1322.021.
The aim of our work was to detect minor loci acting as Alzheimer's disease (AD) genetic markers. We divided 206 AD patients and 186 individuals as controls into six age at onset/age-dependent groups. We studied polymorphisms of the genes of apolipoprotein E (APOE) and its promoter, cathepsin D, butyrylcholinesterase, cystatin C, methionine synthase, and cystathionine beta-synthase. Our results demonstrated that data analysis according to age at onset allows the detection of minor genetic risk factors for AD. Thus, the Th1/E47cs-G allele was an independent AD risk factor after 80 years, whereas the catD-T, BChE-K, CBS-844ins68, and CBS-VNTR 19 alleles are independent AD risk factors after 75 years. On the other hand, the CST3-A allele was an independent AD risk factor before 60 years while the CBS-VNTR allele 21 was an independent AD risk factor before 64 years. In contrast, the MS-AA genotype was an AD risk factor unrelated to age at onset. In conclusion, two main tasks remain to be accomplished to facilitate early detection of people at risk of developing AD: (1) the establishment of common criteria to carry out association studies for different genetic markers, including the introduction of AD age at onset as a crucial variable in each study, and (2) the definition of global and population-specific genetic markers for each age at onset AD subgroup.
我们研究的目的是检测作为阿尔茨海默病(AD)遗传标志物的微小基因座。我们将206例AD患者和186例作为对照的个体分为六个发病年龄/年龄相关组。我们研究了载脂蛋白E(APOE)及其启动子、组织蛋白酶D、丁酰胆碱酯酶、胱抑素C、甲硫氨酸合酶和胱硫醚β合酶的基因多态性。我们的结果表明,根据发病年龄进行数据分析能够检测出AD的微小遗传风险因素。因此,Th1/E47cs - G等位基因在80岁后是独立的AD风险因素,而组织蛋白酶D - T、丁酰胆碱酯酶 - K、胱硫醚β合酶 - 844ins68和胱硫醚β合酶 - VNTR 19等位基因在75岁后是独立的AD风险因素。另一方面,胱抑素C - A等位基因在60岁前是独立的AD风险因素,而胱硫醚β合酶 - VNTR等位基因21在64岁前是独立的AD风险因素。相比之下,甲硫氨酸合酶 - AA基因型是与发病年龄无关的AD风险因素。总之,为促进对有患AD风险人群的早期检测,仍有两项主要任务有待完成:(1)建立通用标准以开展针对不同遗传标志物的关联研究,包括在每项研究中引入AD发病年龄作为关键变量;(2)为每个发病年龄的AD亚组定义全球和特定人群的遗传标志物。