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Association study of late onset Alzheimer's disease with APOC-II gene

晚发性阿尔茨海默病与APOC-II基因的关联研究

基本信息

批准号：
06670986
负责人：
YONEDA Hiroshi
金额：
$ 1.41万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1996
项目状态：
已结题

项目摘要

Pericak-Vance (1991) reported that late-onset familial Alzheimer's disease (AD) was linked to the long arm of chromosome 19. Schellenberg (1992) also reported that apolipoproteinC-II (ApoC-II) gene on the chromosome 19q13.2 region was linked with not early-onset but late-onset familial AD.APOC-II contained four exons and three introns and the 3rd intron was composed of minisatellites. It was found that a two-allele polymorphism in the 3rd intron, whose DNA sequence basis was a variation in the number of tandem repeats of a 40 base tau-like core sequence ; a 375 bp fragment corresponded to an allele with 7 repeat units (allele 1) while a 335bp fragment corresponded to an allele with 6 repeat units (allele 2). We investigated an association between APOC-II and sporadic late-onset AD.The subjects were 33 late-onset AD cases diagnosed according to the criteria of NINCDS-ADRDA and 92 normal controls. We extracted DNA from blood samples and amplified the intron 3 of the APOC-II by PCR.PCR products were electrophoresed in 3% agarose gel and stained by ethidium bromide. We detected the two bands : 375bp (allele 1) and 335bp (allele 2). Thses two bands suggest the existence of genotyper ; 1-1,1-2,2-2. The allele frequencies and the frequencies of genotypes of the controls were not significantly different from those expected from the Hardy-Weinberg equilibrium. The frequency of genotype 1-2 was significantly higher in the late-onset AD patients than in the controls. The frequency of allele 1 was higher in the late-onset patients than in the cotrols. A positve association between APOC-II and sporadic late-onset AD was found. This finding is consistent with earlier association studies with APOC-II polymorphism by Schellenberg (1992). The association we report here indicates that the DNA region with susceptibility to late-onset AD lies APOC-II at the chromosome 19q13.2.

Pericak-Vance（1991）报道晚发型家族性阿尔茨海默病（AD）与19号染色体长臂有关。谢伦贝格（1992）也报道了染色体19 q13.2区域的载脂蛋白C-Ⅱ（ApoC-II）基因与早发性而非晚发性家族性AD连锁。结果发现，第3内含子存在两个等位基因多态性，其DNA序列基础是一个40碱基的tau样核心序列的串联重复数目的变化，其中375 bp的片段对应于一个7个重复单位的等位基因（等位基因1），而335 bp的片段对应于一个6个重复单位的等位基因（等位基因2）。我们研究了APOC-Ⅱ与散发性晚发性AD的关系。研究对象为33例根据NINCDS-ADRDA标准诊断的晚发性AD患者和92名正常对照。提取血样DNA，PCR扩增APOC-Ⅱ基因内含子3，PCR产物经3%琼脂糖凝胶电泳、溴化乙锭染色后，进行测序。结果显示，在该家系中，共检测到两条带：375 bp（等位基因1）和335 bp（等位基因2）。这两条带提示存在1- 1，1 - 2，2 -2基因型。对照组的等位基因频率和基因型频率与Hardy-Weinberg平衡的预期值无显著差异。晚发性AD患者基因型1-2的频率显著高于对照组。晚发型患者等位基因1频率高于对照组。发现APOC-Ⅱ与散发性晚发性AD呈正相关，这一发现与谢伦贝格（1992）关于APOC-Ⅱ多态性的早期关联研究一致。我们在这里报告的关联表明，对迟发性AD易感的DNA区域位于染色体19q13.2上的APOC-II。