日本晚发性阿尔茨海默病患者载脂蛋白E基因及其周围区域的遗传关联研究。
Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese.
作者信息
Takei Norihiro, Miyashita Akinori, Tsukie Tamao, Arai Hiroyuki, Asada Takashi, Imagawa Masaki, Shoji Mikio, Higuchi Susumu, Urakami Katsuya, Kimura Hideo, Kakita Akiyoshi, Takahashi Hitoshi, Tsuji Shoji, Kanazawa Ichiro, Ihara Yasuo, Odani Shoji, Kuwano Ryozo
机构信息
Department of Molecular Genetics, Bioresource Science Branch, Center for Bioresources, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
出版信息
Genomics. 2009 May;93(5):441-8. doi: 10.1016/j.ygeno.2009.01.003. Epub 2009 Feb 3.
The epsilon4 allele of APOE is a well-characterized genetic risk factor for late-onset Alzheimer disease (LOAD). Nevertheless, using high-density single nucleotide polymorphisms (SNPs), there have only been a few studies involving genetic association and linkage disequilibrium (LD) analyses of in and around the APOE. Here, we report fine mapping of a genomic region (about 200 kb) including the APOE in Japanese using 260 SNPs (mean intermaker distance, 0.77 kb). A case-control study demonstrated that 36 of these SNPs exhibited significance after adjustment for multiple testing. These SNPs are located in a genomic region including four genes, PVRL2, TOMM40, APOE and APOC1. Recombination rate estimation revealed that the associated region is firmly sandwiched between two recombination hotspots. Strong LD between these SNPs was observed (mean |D'|=0.914). These data suggest that the three genes other than APOE, i.e. PVRL2, TOMM40 and APOC1, could also yield a predisposition to LOAD.
APOE的ε4等位基因是晚发型阿尔茨海默病（LOAD）一个特征明确的遗传风险因素。然而，利用高密度单核苷酸多态性（SNP），仅有少数研究涉及APOE内部及其周围区域的遗传关联和连锁不平衡（LD）分析。在此，我们报告了使用260个SNP（平均基因座间距为0.77 kb）对日本人群中包含APOE的一个基因组区域（约200 kb）进行精细定位的研究结果。一项病例对照研究表明，在进行多重检验校正后，这些SNP中有36个显示出显著性。这些SNP位于一个包含四个基因PVRL2、TOMM40、APOE和APOC1的基因组区域内。重组率估计显示，关联区域被两个重组热点紧密夹在中间。观察到这些SNP之间存在强连锁不平衡（平均|D'| = 0.914）。这些数据表明，除APOE外的其他三个基因，即PVRL2、TOMM40和APOC1，也可能导致LOAD易感性。
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