Genetic association between polymorphisms of Pen2 gene and late onset Alzheimer's disease in the North Chinese population
Genetic association between polymorphisms of Pen2 gene and late onset Alzheimer's disease in the North Chinese population
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Pen2基因多态性与中国北方人群迟发性阿尔茨海默病的遗传关联
DOI：
10.1016/j.brainres.2007.01.005
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发表时间：
2007-04-13
期刊：
影响因子：
2.9
通讯作者：
Jia, Jianping
中科院分区：
文献类型：
--
作者：
Jia, Longfei;Ye, Jing;Jia, Jianping
早老素增强子 2 (Pen2) 是 γ-分泌酶复合物的一个亚基，可裂解淀粉样蛋白前体蛋白 (APP)，生成淀粉样蛋白 β (Aβ)。我们使用直接测序对所有 Pen2 外显子和内含子进行了系统筛查，以评估其在发展迟发性阿尔茨海默病 (LOAD) 风险中的作用。本研究招募了 947 名受试者（负荷：467；对照：480）。我们获得了三个多态性：rs10402601、rs3817622和rs2293688。在这三个多态性中，rs3817622和载脂蛋白E（APOE）基因型之间存在相互作用（P=0.002）。在携带 APOE 4 等位基因的受试者中，LOAD 组和对照组之间的等位基因分布 (P = 0.003) 和基因型分布 (P = 0.007) 存在显着差异。以等位基因 T 和基因型 T/T 为参考，等位基因 A 和 T/A+A/A 基因型的 OR [95% 置信区间 (CI)] 分别为 4.720 (1.517-10.654) 和 3.886 (1.381-10.932)。我们的结果表明，rs3817622 与中国北方人群中 APOE epsilon 4 携带者的 LOAD 发展之间存在关联。 Pen2 基因的等位基因 A 可能会增加 LOAD 的风险。 (c) 2007 Elsevier B.V. 保留所有权利。
Presenilin enhancer 2 (Pen2) is a subunit of the gamma-secretase complex which cleaves amyloid precursor protein (APP) to generate amyloid beta (A beta). We performed a systematic screening of all Pen2 exons and introns using direct sequencing to assess its role in the risk of developing late onset Alzheimer's disease (LOAD). 947 subjects (LOAD: 467; Controls: 480) were recruited for this study. We obtained three polymorphisms: rs10402601, rs3817622, and rs2293688. Among these three polymorphisms, there was an interaction between rs3817622 and apolipoprotein E (APOE) genotypes (P=0.002). In the subjects with APOE 4 allele, there was a significant difference in the distribution of alleles (P = 0.003) and genotypes (P = 0.007) between LOAD and control groups. ORs [95% confidence interval (CI)] of allele A and T/A+A/A genotypes were respectively 4.720 (1.517-10.654) and 3.886 (1.381-10.932) with allele T and genotype T/T as a reference. Our results suggest that there is an association between rs3817622 and the development of LOAD in APOE epsilon 4 carriers within the northern Chinese population. It is possible allele A of the Pen2 gene increases the risk for LOAD. (c) 2007 Elsevier B.V. All rights reserved.