Piscopo Paola, Manfredi Antonella, Malvezzi-Campeggi Lorenzo, Crestini Alessio, Spadoni Ornella, Cherchi Rossella, Deiana Emiliano, Piras Maria Rita, Confaloni Annamaria
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, 00161 Rome, Italy.
Neurosci Lett. 2006 May 1;398(1-2):124-8. doi: 10.1016/j.neulet.2005.12.063. Epub 2006 Jan 19.
We describe the genetic analysis of an Alzheimer's disease (AD) sample derived from a genetically isolated population. Genetic assessment included the analysis of genes involved in AD, such as the genes for amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). We also assessed genes for some proteins that constitute the gamma-secretase complex: nicastrin (NCSTN), presenilin enhancer-2 (PEN2), in addition to the AD risk factor apolipoprotein E (APOE). Using polymerase chain reaction and single strand conformational polymorphism method, screens for APP, PSEN1 and PSEN2 genes revealed one mutation in PSEN1. Furthermore, we found an intronic +17G>C polymorphism in PEN2 which, in homozygous form, was greater in early onset Alzheimer's disease (EOAD) compared to controls, and one haplotype in the NCSTN gene which was linked to EOAD and familial AD (FAD). Finally, the genotyping of APOE confirmed that the varepsilon4 allele could be a risk factor for the onset of AD, in particular for FAD subjects. In conclusion, these results show the existence of Sardinian genetic peculiarities, essential in studies regarding genetically inherited and multifactorial disorders, as AD.
我们描述了对源自一个基因隔离人群的阿尔茨海默病（AD）样本的基因分析。基因评估包括对参与AD的基因的分析，如淀粉样前体蛋白（APP）、早老素1（PSEN1）和早老素2（PSEN2）的基因。我们还评估了构成γ-分泌酶复合物的一些蛋白质的基因：尼卡斯特林（NCSTN）、早老素增强子2（PEN2），以及AD风险因子载脂蛋白E（APOE）。使用聚合酶链反应和单链构象多态性方法，对APP、PSEN1和PSEN2基因的筛查在PSEN1中发现了一个突变。此外，我们在PEN2中发现了一个内含子+17G>C多态性，纯合形式在早发型阿尔茨海默病（EOAD）中比对照组更为常见，并且在NCSTN基因中发现了一个与EOAD和家族性AD（FAD）相关的单倍型。最后，APOE基因分型证实ε4等位基因可能是AD发病的一个风险因子，特别是对于FAD患者。总之，这些结果表明撒丁岛存在基因特性，这在关于遗传性和多因素疾病（如AD）研究中至关重要。
