Genetic association studies between Alzheimer's disease and two polymorphisms in the low density lipoprotein receptor-related protein gene
Genetic association studies between Alzheimer's disease and two polymorphisms in the low density lipoprotein receptor-related protein gene
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DOI：
10.1016/s0304-3940(98)00141-4
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发表时间：
1998-03-13
影响因子：
2.5
通讯作者：
DeKosky, ST
中科院分区：
文献类型：
--
作者：
Kamboh, MI;Ferrell, RE;DeKosky, ST
载脂蛋白E （APOE）的E*4等位基因是阿尔茨海默病（AD）的主要危险因素，但其潜在机制尚不清楚。低密度脂蛋白受体相关蛋白（LRP）直接参与APOE代谢，因此可能改变APOE相关AD的风险。LRP基因中存在两种常见的多态性，即5'区域的四核苷酸重复和外显子3的同义突变。三项研究报道了四核苷酸多态性与AD的相互矛盾的关联。唯一的外显子3多态性研究发现与AD有显著关联。在这项研究中，我们研究了这两种LRP多态性与散发性晚发性AD的关系。四核苷酸多态性与AD无显著相关性。LRP外显子3多态性的总体基因型和等位基因频率在AD病例和对照组之间具有可比性，但TT基因型的频率在AD对照组中显著高于AD（5.7%比2.5%,P < 0.01）。按APOE基因型分层的数据表明，TT基因型的保护作用仅限于APOE*4携带者。尽管外显子3多态性在我们样本中的影响与之前的研究相比很小，但这需要进一步的研究来证实这种假定的关联。(C) 1998爱思唯尔科学爱尔兰有限公司
The E*4 allele of apolipoprotein E (APOE) is a major risk factor for Alzheimer's disease (AD) but the underlying mechanism is unknown. The low density lipoprotein receptor-related protein (LRP) is directly involved in APOE metabolism and therefore may alter the risk of AD associated with APOE. Two common polymorphisms, a tetranucleotide repeat in the 5'-region and a same-sense mutation in exon 3, are present in the LRP gene. Three studies have reported conflicting association of the tetranucleotide polymorphism with AD. The only study of the exon 3 polymorphism found a significant association with AD. In this study we examined the association of these two LRP polymorphisms with sporadic late-onset AD. No significant association was observed between the tetranucleotide polymorphism and AD. While the overall genotype and allele frequencies for the LRP exon 3 polymorphism were comparable between AD cases and controls, the frequency of the TT genotype was significantly higher in controls than AD (5.7% vs. 2.5%; P < 0.01). Stratification of the data by APOE genotypes indicated that the protective effect associated with the TT genotype was confined to APOE*4 carriers. Although the effect of the exon 3 polymorphism in our sample is small compared to the previous study, this warrants additional studies to confirm this putative association. (C) 1998 Elsevier Science Ireland Ltd.