The genetic basis of peripheral arterial disease: current knowledge, challenges, and future directions.
The genetic basis of peripheral arterial disease: current knowledge, challenges, and future directions.
复制标题
DOI：
10.1161/circresaha.116.303518
复制
发表时间：
2015-04-24
影响因子：
20.1
通讯作者：
Leeper NJ
中科院分区：
文献类型：
--
作者：
Kullo IJ;Leeper NJ
动脉粥样硬化性外周动脉疾病 (PAD) 的几个危险因素，如血脂异常、糖尿病和高血压，都是可遗传的。然而，PAD 的易感性可能受到独立于这些危险因素的遗传变异的影响。识别此类遗传变异将有助于深入了解潜在的病理生理机制，并促进新的诊断和治疗方法的开发。与冠心病相比，影响 PAD 易感性的基因变异相对较少。这可能部分归因于 PAD 更大的临床和遗传异质性。在这篇综述中，我们 a) 提供了有关 PAD 遗传基础的最新知识状况，包括家族研究和候选基因、连锁以及全基因组关联研究的结果； b) 强调研究 PAD 遗传基础的挑战以及克服这些挑战的可能策略； c) 讨论基因组测序、RNA 测序、差异基因表达、表观遗传分析和系统生物学在增加我们对 PAD 分子遗传学的理解方面的潜力。
Several risk factors for atherosclerotic peripheral arterial disease (PAD) such as dyslipidemia, diabetes and hypertension, are heritable. However, predisposition to PAD may be influenced by genetic variants acting independently of these risk factors. Identification of such genetic variants will provide insights into underlying pathophysiologic mechanisms and facilitate the development of novel diagnostic and therapeutic approaches. In contrast to coronary heart disease, relatively few genetic variants that influence susceptibility to PAD have been discovered. This may be in part due to greater clinical and genetic heterogeneity in PAD. In this review, we a) provide an update on the current state of knowledge about the genetic basis of PAD including results of family studies and candidate gene, linkage as well as genome-wide association studies; b) highlight the challenges in investigating the genetic basis of PAD and possible strategies to overcome these challenges; and c) discuss the potential of genome sequencing, RNA sequencing, differential gene expression, epigenetic profiling and systems biology in increasing our understanding of the molecular genetics of PAD.