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KIAA1462 是冠心病相关基因,也是 APOE 携带者晚发性阿尔茨海默病的候选基因。

KIAA1462, a coronary artery disease associated gene, is a candidate gene for late onset Alzheimer disease in APOE carriers.

机构信息

Center for Human Genetics Research and Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America.

Miami Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.

出版信息

PLoS One. 2013 Dec 12;8(12):e82194. doi: 10.1371/journal.pone.0082194. eCollection 2013.

Abstract

Alzheimer disease (AD) is a devastating neurodegenerative disease affecting more than five million Americans. In this study, we have used updated genetic linkage data from chromosome 10 in combination with expression data from serial analysis of gene expression to choose a new set of thirteen candidate genes for genetic analysis in late onset Alzheimer disease (LOAD). Results in this study identify the KIAA1462 locus as a candidate locus for LOAD in APOE4 carriers. Two genes exist at this locus, KIAA1462, a gene associated with coronary artery disease, and "rokimi", encoding an untranslated spliced RNA The genetic architecture at this locus suggests that the gene product important in this association is either "rokimi", or a different isoform of KIAA1462 than the isoform that is important in cardiovascular disease. Expression data suggests that isoform f of KIAA1462 is a more attractive candidate for association with LOAD in APOE4 carriers than "rokimi" which had no detectable expression in brain.

摘要

阿尔茨海默病(AD)是一种破坏性的神经退行性疾病,影响着超过 500 万的美国人。在这项研究中,我们使用了来自 10 号染色体的最新遗传连锁数据,结合基因表达序列分析的数据,选择了一组新的 13 个候选基因,用于对迟发性阿尔茨海默病(LOAD)的遗传分析。本研究的结果确定了 KIAA1462 基因座是 APOE4 携带者中 LOAD 的候选基因座。该基因座存在两个基因,KIAA1462,与冠状动脉疾病相关的基因,以及“rokimi”,编码未翻译的剪接 RNA。该基因座的遗传结构表明,该关联中重要的基因产物要么是“rokimi”,要么是与心血管疾病相关的 KIAA1462 的不同异构体。表达数据表明,KIAA1462 的异构体 f 比在大脑中没有检测到表达的“rokimi”更有可能与 APOE4 携带者中的 LOAD 相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0e6/3861372/673657c0445b/pone.0082194.g001.jpg

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