Tabira T
National Institute of Neuroscience, NCNP, Tokyo.
Rinsho Shinkeigaku. 1997 Dec;37(12):1095-6.
We examined mutations of presenilin 1 (PS1), presenilin 2 (PS2) and amyloid precursor protein (APP) in 30 Japanese familial Alzheimer's disease (FAD) and 34 isolated cases of Alzheimer's disease (AD). We found mutations of PS1 in 17% of early onset FAD (H163R, H163R, R269H, E273A, G384A) and in a case (H163R) of isolated AD. The remaining cases were free from mutations in PS1, PS2 and APP. Since only a part of them could he explained by ApoE epsilon 4, we concluded that important genes are missing. We also examined association of apolipoprotein E (ApoE)epsilon 4, allele A of alpha 1-antichymotrypsin (ACT), 5 repeat allele of very low density lipoprotein receptor (VLDLR) and Alzheimer's disease. We confirmed that ApoE espilon 4 is significantly more frequent in both FAD and isolated AD cases than controls. We could not see any significant association in the ACT polymorphism. The 5 repeat allele of VLDLR was slightly but significantly more frequent in AD cases than controls. However, association with ApoE epsilon 4 was not seen in our study.
我们检测了30例日本家族性阿尔茨海默病（FAD）和34例散发性阿尔茨海默病（AD）患者早老素1（PS1）、早老素2（PS2）和淀粉样前体蛋白（APP）的突变情况。我们在17%的早发型FAD患者中发现了PS1突变（H163R、H163R、R269H、E273A、G384A），在1例散发性AD患者中也发现了PS1突变（H163R）。其余病例在PS1、PS2和APP中均未发现突变。由于其中只有一部分病例可以用载脂蛋白E（ApoE）ε4来解释，我们得出结论，还有重要的基因尚未被发现。我们还研究了载脂蛋白E（ApoE）ε4、α1 -抗糜蛋白酶（ACT）的A等位基因、极低密度脂蛋白受体（VLDLR）的5重复等位基因与阿尔茨海默病的关联。我们证实，在FAD和散发性AD病例中，ApoE ε4的频率均显著高于对照组。我们未发现ACT基因多态性与疾病有任何显著关联。VLDLR的5重复等位基因在AD病例中的频率略高于对照组，但差异有统计学意义。然而，在我们的研究中未发现其与ApoE ε4存在关联。
