https://scholars.lib.ntu.edu.tw/handle/123456789/630127
標題: | Genome-Wide Copy Number Variation Association Study of Atrial Fibrillation Related Thromboembolic Stroke | 作者: | Hsieh, Chia-Shan PANG-SHUO HUANG SHENG-NAN CHANG CHO-KAI WU JUEY-JEN HWANG ERIC YAO-YU CHUANG CHIA-TI TSAI |
關鍵字: | atrial fibrillation;copy number variation;genome-wide;thromboembolic stroke | 公開日期: | 9-三月-2019 | 出版社: | MDPI | 卷: | 8 | 期: | 3 | 起(迄)頁: | 332 | 來源出版物: | Journal of clinical medicine | 摘要: | Atrial fibrillation (AF) is a common cardiac arrhythmia and is one of the major causes of ischemic stroke. In addition to the clinical factors such as CHADS2 or CHADS2-VASC score, the impact of genetic factors on the risk of thromboembolic stroke in patients with AF has been largely unknown. Single-nucleotide polymorphisms in several genomic regions have been found to be associated with AF. However, these loci do not contribute to all the genetic risks of AF or AF related thromboembolic risks, suggesting that there are other genetic factors or variants not yet discovered. In the human genome, copy number variations (CNVs) could also contribute to disease susceptibility. In the present study, we sought to identify CNVs determining the AF-related thromboembolic risk. Using a genome-wide approach in 109 patients with AF and thromboembolic stroke and 14,666 controls from the Taiwanese general population (Taiwan Biobank), we first identified deletions in chromosomal regions 1p36.32-1p36.33, 5p15.33, 8q24.3 and 19p13.3 and amplifications in 14q11.2 that were significantly associated with AF-related stroke in the Taiwanese population. In these regions, 148 genes were involved, including several microRNAs and long non-recoding RNAs. Using a pathway analysis, we found deletions in GNB1, PRKCZ, and GNG7 genes related to the alpha-adrenergic receptor signaling pathway that play a major role in determining the risk of an AF-related stroke. In conclusion, CNVs may be genetic predictors of a risk of a thromboembolic stroke for patients with AF, possibly pointing to an impaired alpha-adrenergic signaling pathway in the mechanism of AF-related thromboembolism. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/630127 | ISSN: | 2077-0383 | DOI: | 10.3390/jcm8030332 |
顯示於: | 醫學系 |
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